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S0014483519307730 | Optic nerve head neuroretinal rim thickness quantified as minimum rim width is a sensitive measure for assessing early glaucomatous disease . The BMO MRW is sensitive to transient fluctuations in intraocular pressure but the time course over which BMO MRW decreases and recovers with changes in IOP remains unknown . The goal of this study was to investigate the dynamics of BMO MRW changes over 2 h periods of mild or moderate IOP elevation and subsequent recovery in healthy non human primate eyes . Eight non human primates were included in the study . For each animal in two different sessions separated by at least 2 weeks the anterior chamber IOP of one eye was maintained at either 25mmHg or 40mmHg for 2h and subsequently at 10mmHg for 2h . For the duration of anterior chamber cannulation optical coherence tomography radial scans centered on the ONH were acquired every 5min and used to quantify BMO MRW . An exponential decay or rise to maximum function was used to determine the extent and rate of structural change . Additionally Bruch s membrane opening area BMO height displacement and BMO referenced anterior lamina cribrosa surface depth were computed from radial scans . A circular scan was used to quantify retinal nerve fiber layer thickness and circumpapillary choroid thickness . The primary results demonstrated that the BMO MRW changed over an extended duration while BMO displacement was rapid and remained stable with sustained IOP . The mean maximum predicted BMO MRW thinning following 2h of IOP elevation was significantly related to pressure . The half life for BMO MRW thinning was 21.99.2min for 25mmHg and 20.94.2min for 40mmHg not significantly different between IOP levels . Subsequently after 2h of IOP at 10mmHg all animals exhibited partial recovery of BMO MRW with similar degrees of persistent residual thinning for the two IOP levels . Similar to BMO MRW choroid thickness exhibited gradual thinning with IOP elevation and residual thinning following IOP reduction . However there was no significant change in BMO area or BMO ALCSD in either experimental session . The RNFLT gradually decreased over the duration of IOP elevation with continued decreases following IOP reduction for the 40mmHg session resulting in total changes from baseline of 2.240.81 and 2.451.21m for 25 and 40mmHg respectively . The sum of the results demonstrate that the ONH neural tissue is sensitive to changes in IOP the effects of which are gradual over an extended time course and different for increased vs. decreased pressure . Understanding the duration over which IOP influences BMO MRW has important implications for studies investigating the effects of IOP on the ONH . Additionally individual variability in ONH response to IOP may improve our understanding of the risk and progression of disease . | Changes in intraocular pressure result in rapid changes in the neuroretinal rim. The neuroretinal rim continues to change over a period of 2h with sustained IOP. Residual thinning of the neuroretinal rim persists after 2h of IOP reduction. There is individual variability in the rate and extent of rim tissue thinning. |
S0014483519307754 | IQ domain GTPase activating protein 1 is a multidomain scaffold protein that is involved in cytoskeleton dynamics and tumor metastasis . Although the role of IQGAP1 in various cancers had been reported the function of IQGAP1 in pterygium has not been studied . In this study surgically excised pterygium and control conjunctival tissue from cataract patients were analysed by immunohistochemistry confocal microscopy and Western blot for IQGAP1 expression mast cell counts and microvascular count . Pterygium was clinically divided into mild and severe types according to Tan s classification and Kim s criteria based on translucency and vascularity of the tissue . Greater clinical severity of pterygium was associated with higher expression of IQGAP1 expression . Compared to normal conjunctival tissue severe pterygium had significantly higher IQGAP1 expression which strongly correlated to the number of microvessels and mast cells . Confocal microscopy revealed IQGAP1 colocalization with mast cell and CD31 . IQGAP1 expression was higher in the pterygium body compared to the head . In conclusion the level of IQGAP1 expression was found to be correlated to the clinical severity of pterygium . Mast cells were identified in pterygium and is suspected to be involved in promoting fibrovascular invasion . | IQGAP1 is expressed in both the normal conjunctiva and pterygium. Greater clinical severity of pterygium is correlated with higher IQGAP1 expression. Greater mast cells and microvascular counts are associated with clinical severity of pterygium. |
S0014483519307821 | We aimed to assess the neuroprotective effect of a pyruvate dehydrogenase kinase inhibitor Nov3r after ischemia reperfusion injury in rats . IR injury was induced by applying 150mmHg of intraocular pressure for 50min . Nov3r was orally administered 3h before and 24h after IR injury . TUNEL positive cells increased and immunoreactive RBPMS positive cells decreased in the rat retinas after IR injury . Administration of Nov3r significantly ameliorated the increase in TUNEL positive cells and prevented the RBPMS positive cell decrease . Similarly the number of IR induced Iba1 positive microglial cells was significantly reduced with Nov3r treatment . Among metabolic parameters IR damage induced the elevation of lactate and pyruvate and the reduction of ATP . Oral administration of Nov3r ameliorated these changes . Our data suggest that the Nov3r had a retinal neuroprotective effect in IR injury in rats . This finding suggests that the regulation of pyruvate dehydrogenase activity has potential therapeutic value by enabling metabolic reprograming in diseases associated with ischemic retinal damage such as diabetic retinopathy retinopathy of prematurity retinal vein occlusion ischemic optic neuropathy and glaucoma . | Pyruvate Dehydrogenase Kinase PDK inhibitor Nov3r increased retinal Pyruvate Dehydrogenase PDH activity. Nov3r showed protective effects of RGCs in Ischemia Reperfusion IR induced injury. Nov3r reduced activation of Iba1 positive microglial cells in IR injury. Nov3r ameliorated metabolic dysfunction in rat retinas after IR injury. |
S0014483519307869 | Bombina variegata 8 also known as prokineticin 2 is a potent pro angiogenic factor . However its role in retinal neovascularization remains unknown . In this study we explored the role of Bv8 in the pathogenesis of RNV . We found that the expression of Bv8 was significantly increased in two different models of retinal neovascularization the oxygen induced retinopathy mouse model and the rhodopsin promoter VEGF transgenic mouse model . Neutralization of Bv8 by intravitreal injections of its antibody not only inhibited retinal and subretinal neovascularization but also decreased the mRNA and protein levels of several pro angiogenic factors . Our in vitro assay showed that recombinant human Bv8 protein promoted human retinal microvascular endothelial cells tube formation cell proliferation and vascular endothelial growth factor receptor 1 and receptor 2 expression . Our findings suggest that Bv8 could be used as a novel target for the treatment of RNV related ocular diseases . | The expression of Bombina variegate 8 Bv8 was significantly increased in the retinal neovascularization RNV mouse model. Bv8 neutralizing not only inhibited RNV but also decreased the mRNA and protein level of several pro angiogenic factors. Recombinant human Bv8 protein promoted human retinal microvascular endothelial cells tube formation cell proliferation and VEGFR1 2 expression. |
S0014483519307894 | Cytologic features such as the shape and size of tumor cells can predict metastatic death in uveal melanoma and other cancers but suffer from poor reproducibility . In this study we investigate the interobserver concordance of digital morphometry and correlate the results with BRCA associated protein 1 expression and | Twelve cell size and shape features were analyzed digitally in uveal melanoma. The average number of cells analyzed in each of 27 tumors was 1957 SD 349 . Interobserver concordance was 85 for all morphometric variables 0.700.93 . Tumor nuclei size correlated to BAP 1 protein expression BAP 1 mutation status monosomy 3 and gene expression class. Patients had significantly shorter survival if their tumor cells had large nuclei. |
S0014483519307936 | Keratocytes synthesize stromal proteins and participate in wound healing through successive differentiation into corneal fibroblasts and myofibroblasts . Cultured keratocytes or corneal fibroblasts are also known as non professional phagocytes and innate immune cells . However whether the corneal fibroblasts phagocytize their dead cells and whether the associated innate immunity is enhanced remains unknown . We initially characterized immortalized corneal fibroblast cells with the expression of specific genes . The corneal fibroblasts strongly expressed extracellular matrix molecules | Corneal fibroblast cells are macrophage like fibroblasts. Corneal fibroblasts can engulf dead bacteria processed cellular debris and entire dead cells. Dying and dead cells stimulate corneal fibroblasts to further induce inflammatory factors. |
S001448351930795X | To observe the morphologic and histopathologic changes of femtosecond laser assisted small incision allogenic intrastromal lenticule implantation in monkey corneas . 6 healthy adult monkeys were included . One eye of two monkeys and both eyes of one monkey received femtosecond lenticule extraction with a 4.0 diopter correction . Each extracted refractive donor lenticule was immediately allogeneically transplanted into a corneal stromal pocket created by a femtosecond laser in another monkey s eye . A postoperative two year follow up was performed with slit lamp microscopy corneal topography anterior segment optical coherence tomography and in vivo confocal microscopy . All eyes were enucleated for Hematoxylin Eosin staining and transmission electron microscopy observation . No complications were observed in the follow up period . At postoperative 2 years the corneas remained clear and the lenticules were integrated with the surrounding tissue under slit lamp microscopy . Nerve fiber regeneration was detected in the lenticule layer as observed through confocal microscopy . Corneal power was increased by 1.831.36 D after 2 years which was less than at 6 months . Disordered fibers and decreased keratocytes in the implanted lenticules could be detected under light microscopy and TEM with a clear boundary between the lenticules and the surrounding tissue . Small incision AILI is feasible and safe for reshaping the cornea . Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years . | Small incision allogenic intrastromal lenticule implantation is feasible and safe for reshaping the cornea. Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years. The mechanism of histopathologic change require further investigation. |
S0014483519308012 | Preclinical imaging especially of rodent models plays a major role in experimental ophthalmology . Our aim was to determine if ultrasound can be used to visualize and measure flow dynamics in the retrobulbar vessels supplying and draining the eye and the potential of contrast microbubbles to provide image and measurement enhancement . To accomplish this we used a 128 element 18MHz linear array ultrasound probe and performed plane wave imaging of the eyes of Sprague Dawley rats . Compound images were acquired by emitting unfocused wavefronts at multiple angles and combining echo data from all angles to form individual B scans . Multiple imaging sequences were utilized compounding up to six angles with imaging rate of up to 3000 compound B scans per second and sequence durations from 1.5 to 180s . Data were acquired before and after intravenous introduction of contrast microbubbles . We found the total power of the Doppler signal in the image plane to increase approximately 20 fold after injection of contrast followed by an exponential decay to baseline in about 90s The best fit time constant of the decay averaged 41s . While major vessels and the retinal choroidal complex were evident pre contrast they were dramatically enhanced with contrast present with details such as choroidal arterioles seen only with contrast . Ocular arteriovenous transit time determined from comparative enhancement curves in arteries and veins was approximately 0.2s . In conclusion plane wave ultrasound especially with enhancement by contrast microbubbles offers a means for the study of ocular hemodynamics using the rat eye as a model . | Blood flow in the retrobulbar vessels of the rat eye was visualized using plane wave ultrasound. Spectrograms allowed determination of arterial and venous velocities over the cardiac cycle. Intravenous contrast microbubbles enhanced visualization of blood flow. After initial peak contrast enhancement declined exponentially. Tail vein to eye and arteriovenous ocular transit time were measured. |
S0014483519308024 | Besides apoptosis necrosis can also occur in a highly regulated and genetically controlled manner defined as regulated necrosis which is characterized by a loss of cell membrane integrity and release of cytoplasmic content . Depending on the involvement of its signal pathway regulated necrosis can be further classified as necroptosis ferroptosis pyroptosis and parthanatos . Numerous studies have demonstrated that regulated necrosis is involved in the pathogenesis of many diseases covering almost all organs including the brain heart liver kidney intestine blood vessel eye and skin particularly myocardial infarction and stroke . Most recently growing evidence suggests that multiple types of regulated necrosis contribute to the degeneration of retinal ganglion cells retinal pigment epithelial cells or photoreceptor cells which are the main pathologic features for glaucoma age related macular degeneration or retinitis pigmentosa respectively . This review focuses on the involvement of necroptosis and ferroptosis in these blinding diseases . | Regulated necrosis plays a key role in pathogenesis of blindness diseases. Necroptosis contributes to the death of RGC RPE and cone cells. Ferroptosis contributes to the death of RGC RPE and cone cells. |
S0014483519308036 | Homo sapiens MIR7 3 host gene a long non coding RNA has been reported to be connected with the progression of several tumors and could be served as a prognostic marker . Our study intends to explore the biological function and potential molecular mechanism of MIR7 3HG in Retinoblastoma progression . Two Rb cell lines Y79 and WERI Rb 1 were applied to perform functional assays . Expression of MIR7 3HG in Rb tissues and cells were determined with the support of GEO database and qRT PCR experiment . The effects of MIR7 3HG on cell activity and apoptosis were assessed through cell counting kit 8 and flow cytometry assays respectively . Targeted connections between MIR7 3HG and miR 27a 3p as well as miR 27a 3p and PEG10 were speculated by bioinformatics prediction software and verified by performing dual luciferase assays . Further interrelationships among MIR7 3HG miR 27a 3p and PEG10 were explored through rescue assays . MIR7 3HG overexpression was detected in Rb tissues and cell lines . Depletion of MIR7 3HG reduced the activity of Rb cells and increased the apoptosis of Rb cells and vice versa . In addition further exploration perceived that MIR7 3HG miR 27a 3p and PEG10 generated a competing endogenous RNA mechanism to regulate Rb cells activity and apoptosis . Our results indicated that MIR7 3HG functioned as a ceRNA to up regulate PEG10 expression via sponging miR 27a 3p to promote the proliferation of Rb cells and suppress the apoptosis of Rb cells exhibiting a group of potential target molecules for Rb treatment in the future . | High expression of MIR7 3HG was presented in Rb tissues and cells. MIR7 3HG executed promotion effect in Rb cell development. Associations among MIR7 3HG miR 27a 3p and PEG10 have been affirmed. Connections among PEG10 MIR7 3HG and miR 27a 3p were further identified. MIR7 3HG miR 27a 3p and PEG10 formed a network to promote Rb progression. |
S0014483519308048 | How the absence of gravity affects the physiology of human beings is generating global research interest as space exploration including missions aboard the International Space Station continues to push boundaries . Here we examined changes in retinal microcirculation and visual electrophysiology in mice suspended by their tails to simulate the cephalad movement of blood that occurs under microgravity conditions . Tail suspension was performed with a head down tilt with a recommended angle of 30 . Mice in the control groups were similarly attached to a tether but could maintain a normal position . Morphologically the 15 day tail suspended mice showed retinal microvascular dilation tortuosity and a relatively long fluorescence retention however the average diameter of the major retinal vessels was not notably changed . In addition optical coherence tomography showed their optic nerve head had an increased diameter . However the mice could adapt to the change with microcirculation and the optic nerve head recovering following 30 day tail suspension . Expression of rhodopsin and cone opsins was not notably changed and no retinal apoptotic positive cells were detected between 15 and 30 day tail suspensions . Moreover the three experimental groups of suspended mice showed normal retinal layers and thickness . Functionally following 15 day tail suspension scotopic electroretinograms showed a decline in the oscillatory potentials but not in the b wave simultaneously the peak time of flash visual evoked potential component N | The effects of simulated microgravity on retinal microcirculation remain unknown. The effect of simulated and real microgravity conditions on the optic nerve head is similar. The changes in the electroretinograms may be related to abnormal retinal microcirculation. However the changes are reversible with no permanent injury observed in the retina. Retinal changes must be studied under simulated microgravity and other space like conditions. |
S0014483519308127 | The purpose of this study was to characterize and develop a primate model of chronic retinal neovascularization and vascular leakage that can be employed to assess efficacy of experimental therapeutics targeting retinal ischemic and neovascular diseases . African green monkeys received bilateral intravitreal injection of DL alpha aminoadipic acid following ophthalmic examination color fundus photography fluorescein angiography and optical coherence tomography . Imaging was repeated to evaluate progression and subsequent stabilization of retinal vascular pathology elicited by DLAAA . Aflibercept was administered IVT to assess effects on vascular leakage . Ocular tissue was collected for histopathology and glial fibrillary acidic protein von Willebrand Factor CD105 endoglin VEGF and CD68 immunohistochemistry to study retinal degeneration and vascular remodeling . IVT DLAAA administration resulted in telangiectatic vessel formation as early as two weeks post injection followed by retinal vascular leakage and inner retinal edema . Neovascular lesion progression was evident up to 810 weeks post injection before stabilizing into a vascular leakage state that persisted beyond 90 weeks . Histopathology and immunostaining revealed retinal degeneration and neovascularization increased expression of vWF CD105 endoglin VEGF and CD68 immunoreactivities in addition to Mller cell loss . Aflibercept significantly attenuated vascular leakage for 24 weeks before progressive return of leakage from weeks 48 . Lesions remained responsive to anti VEGF administration at 90 weeks after DLAAA injection . Findings support application of the primate DLAAA induced retinal vascular leakage model for efficacy evaluations of candidate therapeutics and sustained release strategies targeting exudative AMD diabetic retinopathy macular telangiectasia and other retinal ischemic and neovascular diseases . Findings confirm relevance of the DLAAA primate phenotype to understanding shared retinal vascular disease mechanisms and macular susceptibility to vascular and metabolic insults . | DL 2 aminoadipic acid DLAAA induces chronic retinal vascular leakage in primates. DLAAA induces retinal neovascularization and edema followed by atrophy. Vascular leakage responds to anti VEGF therapy before returning after drug washout. DLAAA model enables evaluation of retinal neovascular therapeutic candidates. |
S0014483519308164 | Endothelin 1 a potent vasoconstrictor plays a significant role in the pathophysiology of ocular conditions like glaucoma . Glaucoma is characterized by apoptotic loss of retinal ganglion cells and loss of visual fields and is a leading cause of irreversible blindness . In glaucomatous eyes retinal ischemia causes release of pro inflammatory mediators such as interleukin 1 IL 6 and tumor necrosis factor and promotes activation of transcription factors such as nuclear factor kappa B and c Jun . Magnesium acetyltaurate has previously been shown to protect against ET 1 induced retinal and optic nerve damage . Current study investigated the mechanisms underlying these effects of MgAT which so far remain unknown . | MgAT protects against endothelin 1 induced retinal ganglion cells in rats. MgAT suppresses endothelin 1 induced retinal expression of IL 1 IL 6 and TNF . MgAT suppresses endothelin 1 induced activation of NFKB and c Jun in rat retinas. MgAT protects against endothelin 1 induced changes in visual behaviour of rats. |
S0014483519308218 | Mesenchymal stem cells exhibit beneficial effects on autoimmune dacryoadenitis . However the underlying mechanisms are not fully understood . In this study we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells on rabbit autoimmune dacryoadenitis an animal model of Sjgren s syndrome dry eye and explored whether the effects of MSCs were related to their modulation on macrophage polarization . We have showed that systemic infusion of hUC MSCs after disease onset efficiently diminished the chronic inflammation in diseased LGs and improved the clinical symptoms . Further analysis revealed that hUC MSC treatment significantly inhibited the expression of pro inflammatory M1 macrophage markers iNOS TNF and IL 6 and promoted the expression of anti inflammatory M2 macrophage markers Arg1 CD206 IL 10 IL 4 and TGF in LGs . Mechanistically hUC MSCs activated AKT pathway in macrophages resulting in upregulation of M2 associated molecule Arg1 which was partly abolished by PI3K inhibitor LY294002 . Together our data indicated that hUC MSCs can skew macrophages into an M2 phenotype via affecting AKT pathway . These data may provide a new insight into the mechanisms of hUC MSCs in the therapy of SS dry eye . | HUC MSCs infused after disease onset efficiently attenuated rabbit autoimmune dacryoadenitis. HUC MSC treatment promoted the expression of M2 macrophage associated molecules in diseased LGs. HUC MSCs modulated M2 macrophage polarization via activating AKT pathway. |
S0014483519308383 | Vitreous liquefactive processes play an integral role in ocular health . Knowledge of the degree of liquefaction would allow better monitoring of ocular disease progression and enable more informed therapeutic dosing for an individual patient . Presently this process can not be monitored in a non invasive manner . | MRI protocol optimisation allows acquisition of homogenous T2 maps of artificial vitreous humour. Artificial vitreous humour T2 can be correlated with viscoelastic properties of the gel. An optimised MRI protocol can non invasively identify regional variations in T2 within porcine vitreous humour . |
S0014483519308462 | Diabetic retinopathy is considered as a diabetes related complication that can lead to severe visual impairments . By 2030 it is expected that 1 in 5 adults will suffer from the disease . Suitable animal models for chronic DR are essential for a better understanding of the pathophysiology and to further develop new treatments . | Reliable DR animal models that reproduce the whole spectrum of the disease are crucial to the development of new therapies. Ins2. mouse model develops an inflammatory response in the retina predominantly in early stages of DR. Ins2. mouse model shows a dysregulation in pro and antiangiogenic factors in the retina. |
S0014483519308474 | Preeclampsia is a hypertensive complication of pregnancy . Its cause is still unknown and it could be a risk factor for future ophthalmic problems . Retinal vascular bed alterations have been described as a consequence of PE suggesting a retinopathy . Factors related to angiogenesis and vascular permeability such as vascular endothelial growth factor and pigment epithelium derived factor or components of the renin angiotensin aldosterone system prorrenin renin receptor RR and angiotensin II type I receptor have been located in the retina participating in other retinopathies but it is unknown if they could participate in PE . Our aim was to elucidate whether VEGF PEDF RR and AT1R could be modified during PE and during hypertension induced in rats with a history of PE . We used female Wistar rats and subrrenal aortic coarctation to induce PE and after delivery we induced a second hit by N nitro L arginine methyl ester administration . We measured blood pressure proteinuria and pups development . In both models eye fundal exploration and immunoblot for VEGF PEDF RR and AT1R were performed . We found that the development of hypertension occurred faster in previously PE rats than in normal animals . VEGF PEDF RR and AT1R were increased in PE but in L NAME induced hypertension only RR and AT1R were altered . Eye fundal data indicated that PE induced a level I retinopathy but L NAME induced a faster and more severe retinopathy in previously PE animals compared to previously normal pregnancy rats . These results indicate that PE predisposes to development of a faster and more severe retinopathy after a second hit . They also suggest that VEGF and PEDF seem to participate only in PE retinopathy but in both models RAAS components seem to have a more critical participation . | AT1 receptor and Pro renin renin receptor participates in preeclampsia retinopathy. VEGF and PEDF are augmented in preeclamptic retinopathy. L NAME induced hypertension develops faster in previously preeclamptic animals. AT1 receptor and Pro renin renin receptor participate in L NAME induced retinopathy. VEGF and PEDF do not seem to participate in L NAME induced retinopathy. |
S0014483519308619 | There is accumulating evidence that aging shifts the central nervous system milieu towards a proinflammatory state with increased reactivity of microglia in the aging eye and brain having been implicated in the development of age related neurodegenerative conditions . Indeed alterations to microglial morphology and function have been recognized as a part of normal aging . Here we sought to assess the effects of age on the retinal microglial and macrophage response to acute intraocular pressure elevation . Further we performed experiments whereby bone marrow from young or middle aged mice was used to reconstitute the bone marrow of whole body irradiated 12 month old mice . Bone marrow chimeric mice then underwent cannulation and IOP elevation 8 weeks after whole body irradiation and bone marrow transplantation in order to determine whether the age of bone marrow alters the macrophage response to retinal injury . Our data show retinal macrophage reactivity and microglial morphological changes were enhanced in older mice when compared to younger mice in response to injury . When IOP elevation was performed after whole body irradiation and bone marrow rescue we noted subretinal macrophage accumulation and glial reactivity was reduced compared to non irradiated mice that had also undergone IOP elevation . This effect was evident in both groups of chimeric mice that had received either young or middle aged bone marrow suggesting irradiation itself may alter the macrophage and glial response to injury rather than the age of bone marrow . | Retinal macrophage reactivity was enhanced in older mice following IOP elevation. Retinal macrophage responses to injury were altered in chimeric mice. Gliosis was attenuated following IOP elevation in chimeric mice. Altered macrophage responses in chimeric mice was independent of bone marrow age. Irradiation may alter macrophage and glial responses after injury. |
S0014483519308668 | Sudden acquired retinal degeneration syndrome in dogs is proposed to have an immune mediated etiology . However there is conflicting evidence regarding the presence of antiretinal antibodies as assessed by western blotting in the serum of SARDS patients . Because of the possibility that antibodies recognize only conformational epitopes we hypothesized that a more sensitive method to investigate circulating retinal autoantibodies in SARDS is immunofluorescence . Sera from 14 dogs with early SARDS and 14 age and breed matched healthy control dogs were screened for circulating antiretinal IgG IgM IgE and IgA using indirect immunofluorescence on lightly fixed frozen sections of normal canine retina . Controls without canine serum were also performed . A nuclear counterstain was used to identify cellular retinal layers . Images were obtained using a fluorescence microscope and 2 3 separate masked observers graded retinal layers for fluorescence staining intensity using a 03 scale . Total circulating IgG and IgM was assessed by radial immunodiffusion . Statistical analysis was performed using 2 way ANOVA paired 2 tailed student s t test and correlation analysis . Intensity of IgG staining of photoreceptor outer segments was significantly higher using serum from dogs with SARDS compared with healthy controls in 2 3 observers | The serum of dogs with SARDS contains anti photoreceptor IgG. Dogs with SARDS have elevated total circulating IgM and reduced total circulating IgG compared with matched controls. Canine SARDS and human AIR have similarities in terms of presence of antiretinal antibodies on indirect immunofluorescence. |
S001448351930870X | We report an analysis of the aqueous humor metabolome of primary open angle glaucoma in comparison to normal controls . The AH samples were obtained from human donors POAG . The AH samples were subjected to one dimensional | We report the metabolites of control versus primary open angle glaucoma POAG aqueous humor AH . We used. H nuclear magnetic resonance NMR and isotopic ratio outlier analysis IROA using a Q Exactive mass spectrometer. There were significant metabolite changes found in the POAG AH. |
S0014483519308735 | The intraepithelial corneal nerves that innervate the corneal epithelium are maintained through interactions with corneal epithelial cells and the extracellular matrix they produce . One to several axons bundle together within the basal cell layer and extend parallel to the ocular surface or branch and extend apically . Here we use 3 dimentional ultrastructural reconstructions of control and trephine injured mouse corneal epithelium and stroma produced using Focused Ion Beam Scanning Electron Microscope to determine whether corneal epithelial or immune cells resident in the epithelium remove axonal debris and degrade it in their lysosomes after trephine injury to the cornea . We demonstrate that axonal fragments are internalized in the corneal epithelium and accumulate within electron dense structures consistent with lysosomes 3h after trephine injury in both epithelial and immune cells located among the basal cells of the trephine injured cornea . Confocal imaging showed fewer CD45 | FIB SEM shows the EBM thinning near sites where ICNs come in close contact. FIB SEM shows debris in lysosomes after trephine injury. Stromal nerves impacted by trephine only injury. Immune cells are reduced at the corneal periphery after trephine injury. |
S0014483519308826 | There is a need to find alternative treatments for MEe . Bromfenac has shown promise in inhibiting the COX 2 enzymatic pathway that partially causes the inflammatory cascade which contributes to the precipitation of ME . However like other NSAID s its intraocular half life is limited . We hypothesize that a delayed release liposome formulation containing bromfenac might provide a similar anti inflammatory effect as long lasting steroid release systems without the well known steroidal side effects . We introduced a novel formulation with these characteristics into the vitreous cavity of rabbit eyes in order to evaluate its safety profile . 10 left eyes of rabbits were injected with the liposome encapsulated bromfenac suspension . Basal ERG s were recorded . Total follow up time was 3 months at which point ERG s were repeated and eyes were enucleated for histopathological study . Total amplitude and implicit times were recorded . A difference of 25 in either recording was considered significant . Significance was assessed using the paired t test and Wilcoxon matched pairs signed rank test . A p value of 0.05 was considered significant . No significant changes were recorded in ERG measurements after 3 months when compared to basal measurements . Histopathological analysis of retinal specimens found no traces of liposome induced toxicity . The liposome encapsulated bromfenac suspension is not toxic and has been proven safe to use in an animal model . Therefore this formulation shows promise as a possible future alternative treatment for ME and should be further studied to show its biological effect and efficacy . | Diabetic macular edema is the main cause of impaired BCVA in developed countries. The pathogenesis of DME is multifactorial but one of the main routes is inflammation. Although Anti VEGF therapy is the gold standard of therapy it is not enough to perfectly handle DME. By attacking the COX 2 pathway of inflammation it is possible to improve the features of DME. Liposome encapsulated bromfenac may be a new therapeutic option for DME. |
S0014483519308863 | Gene therapy has been proposed as a feasible strategy for RGC survival and optic nerve regeneration . Some preclinical and clinical studies revealed intraocular inflammation after intravitreal injection of adeno associated virus by slit lamp or indirect ophthalmoscope . Here we evaluate the longitudinal profile of immediate inflammatory responses after AAV2 injection in rat retina and vitreous body by optical coherence tomography . Adult Fischer F344 rats were intravitreally injected once with saline AAV2 or zymosan . Retinal thickness and cell infiltration were recorded by OCT longitudinally for 2 months and verified by histological analysis . The transduction rate of single intravitreal AAV2 injection was 21.34.9 of whole retina and the transduction efficiency on RGCs was 91.52.5 in the transduced area . Significant increase in cell infiltration was observed from Day 13 after AAV2 injection compared to very few infiltrating cells observed in the saline injected group . The infiltrating cells ceased at Day 5 after intravitreal injection and remained absent at 2 months . The thicknesses of total and inner retina were increased along Day 13 after AAV2 injection but reverted to normal afterwards . The surviving RGCs in the AAV2 injected groups at Day 14 showed no significant difference compared to saline injected group . In summary this study revealed the immediate inflammatory responses and retinal edema after intravitreal AAV2 injection in normal rats without influencing long term retinal thickness and RGC survival . OCT can be implemented for the time lapse | This study revealed the acute inflammatory responses and retinal edema after intravitreal injection of AAV2 mediated gene. Intravitreal injection of AAV2 mediated gene didn t influence RGC survival in normal rats. OCT can help to evaluate the time lapse. inflammatory response of gene therapy. |
S0014483519308930 | The central biological clock system of bird is formed by hypothalamus suprachiasmatic nucleus pineal gland and retina thereby interacting with each other in a neuroendocrine loop . Previous results have confirmed that monochromatic light can influence the clock genes in the pineal gland hypothalamus and retina of chicks in vivo . The present work was conducted to study whether the cultured retinal tissue of chick could maintain the circadian oscillation and whether the monochromatic light affect the expression level of cultured retinal circadian clock in vitro . Retinal tissues of 0 day old chicks were cultured in vitro under 4 light treatments with light dark cycle 12 12 and constant dark . The tissues and culture medium were collected every each 4h . Melanopsin clock genes | The cultured chick retinal tissue was established and the biological clock of retina was affected by the color of light. In constant dark the molecular clock and melatonin in isolated chick retina tissue maintained circadian oscillation. Green light increased melatonin and. by enhancing the circadian expression of melanopsin and positive clock genes. |
S0014483519308966 | Strong communication and interaction between the retinal pigment epithelium and the photoreceptor cells is essential for vision . RPE cells are essential for supporting and maintaining PR cells by transporting nutrients waste products and ions and phagocytosing photoreceptor outer segments . POS phagocytosis follows a circadian pattern taking place in the morning in human mice and other organisms . However it remains unknown whether other RPE processes follow a daily rhythm . To study the daily rhythm of RPE cells we isolated murine RPE cells at six different time points during a 24h period after which RNA was isolated and sequenced . Murine RPE flatmounts were isolated at four different time points to study daily rhythm in protein abundance and localisation . EnrichR pathway analysis resulted in 13 significantly enriched KEGG pathways of which seven showed a large number of overlapping genes . Several genes were involved in intracellular trafficking possibly playing a role in nutrient transport POS phagocytosis or membrane protein trafficking with different expression patterns during the day night cycle . Other genes were involved in actin cytoskeleton building remodelling and crosslinking and showed a high expression in the morning suggesting actin cytoskeleton remodelling at this time point . Finally tight junction proteins Cldn2 and Cldn4 showed a difference in RNA and protein expression and tight junction localisation over time . Our study suggests that several important processes in the RPE follow a day night rhythm including intracellular trafficking and processes involving the actin cytoskeleton and tight junctions . The differential protein localisation of Cldn2 in the RPE during the day night cycle suggest that Cldn2 may facilitate paracellular water and sodium transport during the day . | Cldn2 RNA and protein expression show clear differences over time in RPE cells. Paracellular water and sodium transport in RPE might be facilitated by Cldn2 during the day. Genes involved in intracellular trafficking show differential day night expression. Genes involved in cytoskeleton remodelling show high expression in the morning. |
S0014483519309005 | The complement system may be activated in the posterior segment of the eye with chorioretinal disease which may be reflected to the concentration of anaphylatoxins in the aqueous humor . Little is known about the distribution of anaphylatoxins in the aqueous and vitreous humor . The aim of the present study was to investigate the distribution of anaphylatoxin concentration in the aqueous and vitreous humor of the eyes with idiopathic epiretinal membrane or idiopathic macular hole . This was an experimental observational case series . This study included 43 eyes from 43 patients 29 eyes with idiopathic epiretinal membrane and 14 eyes with idiopathic macular hole . All 43 eyes underwent cataract surgery and vitrectomy . The aqueous and vitreous humor were collected at the surgery . The anaphylatoxin concentrations were measured by using a cytometric beads array and the respective C3a C4a and C5a concentrations were 2.0030.679 ng ml 1.3890.419ng ml and 0.0030.004ng ml in the aqueous humor and 1.2360.642ng ml 1.2500.542ng ml and 0.0480.069ng ml in the vitreous humor . The mean C3a concentration in the aqueous humor was significantly higher than in the vitreous humor in 43 eyes of iMH and iERM . The mean C4a concentration showed no significant difference between the aqueous humor and vitreous humor and the mean C5a in the aqueous humor was significantly lower than in the vitreous humor overall . The C3a concentration in the aqueous humor strongly correlated with that in the vitreous humor . The concentrations of C4a and C5a in the aqueous humor moderately correlated with those in the vitreous humor . In conclusion the anaphylatoxin concentrations measured by cytometric beads array in the aqueous humor may be associated with those measured in the vitreous humor . | Anaphylatoxins were detected in the eyes with idiopathic epiretinal membrane and idiopathic macular hole. The concentration of C3a in the aquous humor was significantly correlated to that in the vitreous humor. Measuring anaphylatoxins in the aqueous humor may be useful to estimate the complement activation in the vitreous. |
S0014483519309029 | Retinopathy of prematurity is a growing cause of lifelong blindness and visual defects as improved neonatal care worldwide increases survival in very low birthweight preterm newborns . Advancing ROP is managed by laser surgery or a single intravitreal injection of anti VEGF typically at 3336 weeks gestational age . While newer methods of scanning and telemedicine improve monitoring ROP the above interventions are more difficult to deliver in developing countries . There is also concern as to laser induced detachment and adverse developmental effects in newborns of anti VEGF treatment spurring a search for alternative means of mitigating ROP . Pigment epithelium derived factor a potent angiogenesis inhibitor appears late in gestation is undetected in 2528 week vitreous but present at full term . Its absence may contribute to ROP upon transition from high to ambient oxygen environment or with intermittent hypoxia . We recently described antiangiogenic PEDF derived small peptides which inhibit choroidal neovascularization and suggested that their target may be laminin receptor 67LR . The latter has been implicated in oxygen induced ischemic retinopathy . Here we examined the effect of a nonapeptide PEDF 336 in a newborn mouse OIR model . Neovascularization was significantly decreased in a dose responsive manner by single intravitreal injections of 1.257.5 g eye . By contrast anti mouse VEGFA | PEDF derived 9 mer peptide PEDF 336 previously shown to inhibit laser induced CNV in mice was tested in OIR. IVT injection of 1 L PEDF 336 1.257.5 g in neonatal mouse eyes at transition from 75 O2 to room air P12 reduced NV and VO at P17. While PEDF 336 displayed dose responsive efficacy anti mouse VEGFA164 was active only at 25 ng eye but not at half or twice this dose. Combination of both peptide and anti VEGF showed only antibody efficacy but not robust peptide activity thus the latter may require VEGF. PEDF 336 contains a 5 mer epitope Y R that binds laminin receptor 67LR which increased on choroidal EC after exposure to VEGF. |
S0014483519309066 | The presence of a phagocytic peak of photoreceptor outer segments by the retinal pigment epithelium one or 2h after the onset of light has been reported for several diurnal and nocturnal species . This peak in phagocytic activity also persists under constant lighting conditions thus demonstrating that the timing of this peak is driven by a circadian clock . The aim of this study was to investigate the change in RPE whole transcriptome at two different circadian times and 1h after subjective light onset . C57BL 6J male mice were maintained in constant dark conditions for three days and euthanized under red light at CT23 and CT1 . RPE was isolated from whole eyes for RNA library preparation and sequencing on an Illumina HiSeq4000 platform . 14 083 mouse RPE transcripts were detected in common between CT23 and CT1 . 12 005 were protein coding transcripts and 2078 were non protein coding transcripts . 2421 protein coding transcripts were significantly upregulated whereas only 3 transcripts were significantly downregulated and 12 non protein coding transcripts were significantly upregulated and 31 non protein coding transcripts were significantly downregulated at CT1 when compared to CT23 . Of the protein coding transcripts most of them were characterized as enzymes kinases and transcriptional regulators with a large majority of activity in the cytoplasm nucleus and plasma membrane . Non protein coding transcripts included biotypes such as long non coding RNAs and pseudogenes . Gene ontology analysis and ingenuity pathway analysis revealed that differentially expressed transcripts were associated with integrin signaling oxidative phosphorylation protein phosphorylation and actin cytoskeleton remodeling suggesting that these previously identified phagocytic pathways are under circadian control . Our analysis identified new pathways that may be involved in the circadian control of phagocytic activity . In addition our dataset suggests a possible regulatory role for the identified non protein coding transcripts in mediating the complex function of RPE phagocytosis . Finally our results also indicate as seen in other tissues about 20 of the whole RPE transcriptome may be under circadian clock regulation . | Identified a new pathway mitochondrial oxidative phosphorylation associated with circadian control of phagocytic activity. About 20 of the whole RPE transcriptome may be under circadian clock regulation. Known RPE phagocytic pathways integrin protein phosphorylation cAMP signaling are possibly under circadian control. Identified 14 083 transcripts where 12 005 were protein coding and 2078 were non protein coding transcripts. Observed large upregulation transcriptional activity at CT1 compared to CT23 2421 with little downregulation activity 3 . |
S0014483519309133 | Scleral fibroblast activation occurs in glaucomatous and myopic eyes . Here we perform an unbiased screen to identify kinase inhibitors that reduce fibroblast activation to diverse stimuli | Scleral biomechanics and collagen ultrastructure are altered in glaucoma. We performed a screen to identify kinase inhibitors that reduce scleral myofibroblast differentiation. The multikinase inhibitor dasatinib reduces scleral myofibroblasts at nanomolar dosages. |
S001448352030004X | Familial exudative vitreoretinopathy is a disease exhibits a wide range of clinical signs ranging mild peripheral retinal vascular anomalies to severe retinal detachments . Individuals with mild FEVR are frequently asymptomatic with good visual function and are often undiagnosed . However little is known about the genetic characters of the cohort . The purpose of this study was to investigate the clinical characteristics and genetic spectrum of in patients with asymptomatic mild FEVR . Herein sixty two patients with asymptomatic mild FEVR were studied in a case series . Comprehensive ophthalmic examinations and genetic testing were performed in all patients . Clinical examinations showed that the avascular zone was seen in all 124 eyes and was the most common abnormality observed . Increased vessel branching and straightened peripheral vessel branches were found in 122 eyes . Late phase angiographic posterior and peripheral leakage was observed in 80 eyes and V shape degeneration was noted in 36 eyes . Other manifestations including extensive anastomoses retinal ridges and extraretinal neovascularization which were detected in 30 10 and 2 eyes respectively . Overall pathogenic mutations were identified in 48.4 of individuals with asymptomatic mild FEVR . Mutations in | First report on the spectrum of genetic mutations in patients with asymptomatic mild FEVR cohort. The clinical and genetic characteristics were analyzed. Ten novel variants were detected. |
S0014483520300130 | Restoration of corneal sensitivity is of utmost importance to maintain corneal homeostasis following any injury or insult for which both corneal nerve regeneration and re innervation are essential . Fibrosis poses a major impediment for re innervation . We have in this study evaluated the influence of various nerve growth factors and corneal fibrosis on corneal nerve regeneration and reinnervation following lamellar flap surgery and its modulation using antifibrotic drug pirfenidone . To achieve this trigeminal ganglion cells were treated with pirfenidone NGF and NT 3 to evaluate their effect on trigeminal cell neurite growth . Following LFS the gene expression of nerve growth factors NGF BDNF and NT 3 Gap 43 Nogo A and profibrotic factors Tenascin C TGF beta 1 were evaluated with and without pirfenidone . Wound fibrosis and corneal nerve regeneration using pirfenidone following LFS were evaluated by staining whole corneal mounts with SMA and tubulin 3 . Safety of NGF and pirfenidone topical drops in normal unoperated cornea and its efficacy in enhancing corneal healing was evaluated following LFS . Our study shows pirfenidone did not influence trigeminal cell neurite elongation NGF and NT 3 significantly enhanced trigeminal cell neurite elongation . NT 3 also significantly increased neurite branching . There was significant increase in the gene expression of NGF BDNF NT 3 Gap 43 TGF beta 1 Tenascin C Nogo A genes in the operated cornea compared to normal cornea treatment of operated corneas with pirfenidone prevented the increased expression of these genes except Gap 43 which remained unchanged . The treatment of operated eyes with combination of NGF and pirfenidone positively influenced corneal healing compared to treatment with NGF alone and had no adverse influence on the cornea . Pirfenidone appreciably reduced corneal fibrosis which aided in re innervation . Both NGF and NT3 positively influence trigeminal neurite elongation . NGF and pirfenidone have complementary influence on corneal wound healing . | Corneal innervation is imperative for corneal homeostasis. Fibrosis can impede the path of corneal nerve re innervation. Pirfenidone does not adversely affect trigeminal neuron cell growth. Topical therapy with pirfenidone and Nerve growth factor are complementary for corneal healing. |
S0014483520300476 | is a common bacterial isolate from cases of microbial keratitis . The virulence factors that contribute to its pathogenicity during this disease have not been fully resolved . The aim of the current study was to examine the effects of the extracellular protease Staphopain A on corneal virulence . Two strains were used one Staph 38 that gives a high pathology score during keratitis and a less virulent strain ATCC 8325 4 . The effect of inhibition of Staphopain by general or specific protease inhibitors on adhesion of strains to fibronectin coated glass or PMMA was determined . This was followed by an analysis of the effect of Staphopain A on the ability of the bacteria to adhere to and invade corneal epithelial cells . Finally the effect of inhibiting Staphopain A on pathogenesis in a mouse model of keratitis was studied . Staphopain A increased the adhesion of strains to fibronectincoated substrata and inhibition of Staphopain A reduced adhesion . The inhibition of Staphopain A by staphostatin A significantly decreased both association with and invasion into human corneal epithelial cells by 15 fold for strain Saur38 . Inhibition of Staphopain A significantly reduced the pathology associated with | The staphylococcal protease staphopain contributes to fibronectin binding. The staphylococcal protease staphopain contributes to pathology during keratitis. Inhibition of staphopain by staphostatin A significantly reduces corneal pathology during keratitis. |
S001448352030049X | Basement membranes are highly specialized extracellular matrices . More than providing scaffolds basement membranes are recognized as dynamic and versatile structures that modulate cellular responses to regulate tissue development function and repair . Increasing evidence suggests that in addition to providing structural support to adjacent cells basement membranes serve as reservoirs and modulators of growth factors that direct and fine tune cellular functions . Since the corneal stroma is avascular and has a relatively low keratocyte density it s likely that the corneal BM is different in composition from the BMs in other tissues . BMs are composed of a diverse assemblage of extracellular molecules some of which are likely specific to the tissue where they function but in general they are composed of four primary componentscollagens laminins heparan sulfate proteoglycans and nidogensin addition to other components such as thrombospondin 1 matrilin 2 and matrilin 4 and fibronectin . Severe injuries to the cornea including infection surgery and trauma may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma . Ultrastructural studies have demonstrated that defective epithelial basement membrane regeneration after injury to the cornea underlies the development of myofibroblasts from both bone marrow and keratocyte derived precursor cells . Defective EBM permits epithelium derived and tear derived transforming growth factor beta platelet derived growth factor and possibly other modulators to penetrate the stroma at sustained levels necessary to drive the development and persistence of vimentin alpha smooth muscle actin desmin mature myofibroblasts . A recent discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts produce critical EBM components such as nidogen 1 nidogen 2 and perlecan that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self polymerizes into a nascent EBM . Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte corneal fibroblast contributions to the nascent EBM . These myofibroblasts and the opacity they produce often persist for months or years after the injury . Transparency is subsequently restored if the EBM is fully regenerated myofibroblasts are deprived of TGF and undergo apoptosis and keratocytes reoccupy the anterior stroma and reabsorb the disordered extracellular matrix . | Major components of the EBM are collagens laminins perlecan and nidogens. Keratocytes and corneal fibroblasts contribute components during EBM regeneration. The EBM regulates the localization of TGF PDGF HGF and KGF. Defective regeneration of the EBM underlies stromal fibrosis. |
S0014483520300543 | We aim to determine whether lymphatic drainage from the eye changes with age . Using quantitative photoacoustic tomography groups of young and older mice were studied in the live state . 10 CD 1 mice of 23 months were studied in addition to 13 older mice of 1213 months . In each of 23 mice near infrared tracer was injected into the right eye and imaging of ipsilateral cervical lymph nodes was performed with laser pulses at 11 different wavelengths prior to and 20min 2 4 and 6h after injection . Mean pixel intensities of nodes were calculated at each imaging session . The areas under the curves were calculated for both groups of mice and compared using the | A novel non invasive photoacoustic imaging approach was used to quantify lymphatic drainage from the eye. Lymphatic drainage from the eye was found to be reduced in older compared to younger mice. Age related decline of ocular lymphatic function and impaired clearance of proteins from the eye may be relevant to the understanding and treatment of age related eye diseases. |
S0014483520300683 | This study aimed to assess the cytotoxic effect of low molecular weight components and conventional silicone oils 1000cSt with different degree of purification using in vitro cytotoxicity tests . Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells using quantitative and qualitative evaluation according to the ISO 10993 5 standards . Conventional SOs 1000cSt in form of raw intermediate and purified SO and a concentrate of LMWC were directly applied to 100 of cell layer area for 24h . Cell viability was quantified using 3 2 528 diphenyltetrazolium bromide and neutral red uptake assays in ARPE 19 and BALB3T3 respectively . All tested samples including the concentrate of LMWC resulted to be not cytotoxic according to ISO 10993 5 in both qualitative and quantitative evaluations . However the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE 19cells . No reduction in cell viability was detected by LMWC . | Silicone oils with various purification degree were not cytotoxicity on BALB3T3 and ARPE 19cells. Low molecular weight components were not cytotoxicity on BALB3T3 and ARPE 19cells. Acute direct cytotoxicity is not likely to influence the biocompatibility of purified SO 1000cSt. |
S001448352030141X | Expression patterns of voltage gated ion channels determine the spatio temporal dynamics of ion currents that supply excitable neurons in developing tissue with proper electrophysiological properties . The purpose of the study was to identify fast cationic inward currents in mouse retinal horizontal cells and describe their biophysical properties at different developmental stages . We also aimed to reveal their physiological role in shaping light responses in adult HCs . HCs were recorded in horizontal slices of wild type mouse retina at postnatal stages ranging from p8 through p60 . Voltage dependent inward currents were isolated with appropriate voltage protocols and blockers specific for sodium and T type calcium channels . LRs were evoked with full field flashes 130W cm | Mouse retinal horizontal cells express T type calcium and sodium channels. Sodium and calcium currents are downregulated during development. Activation and inactivation kinetics of sodium and calcium channels remain similar during development. T type calcium channels contribute to the dark resting membrane potential. Fast ionic currents influence horizontal cell light responses. |
S001448352030292X | Bowman s layer lies immediately posterior to the epithelial basement membrane and anterior to the stroma proper in humans chickens quail zebra fish deer giraffe antelope California sea lions guinea pig and several other species . It is not found in dog wolf cat tiger lions rabbit pigs cows goats or horses . Developmental anomalies of Bowman s layer are rare but acquired damage to Bowman s layer or even complete destruction is frequently seen in advanced bullous keratopathy or Fuchs endothelial dystrophy . No detrimental effects of removal of Bowman s layer over the central 67mm of central cornea have been noted in millions of patients who ve had photorefractive keratectomy . Recent studies have suggested the randomly oriented collagen fibrils that make up Bowman s layer do not have a significant barrier function in modulating the passage of moderate to large sized proteins . It is hypothesized that Bowman s layer develops in the corneas of those species that have one because of cytokine mediated interactions occurring between corneal epithelial cells and underlying keratocytes including negative chemotactic and apoptotic effects on the keratocytes by low levels of cytokines such as interleukin 1 that are gradually released as epithelial cells die and slough during their normal development . A Bowman s like layer can generate around stromal epithelial plugs after radial keratotomy and possibly beneath the central corneal epithelial basement membrane many years after PRK . | Bowman s layer is present in some species and absent in others. Bowman s layer is not a barrier to passage of large molecules. A Bowman s like layer may regenerate after corneal surgery. Bowman s layer likely maintained by ongoing epithelial stromal interactions. |
S0014483520302931 | To characterize microRNAs and their possible roles in high myopia by using next generation sequencing . Aqueous humor samples were obtained from 25 highly myopic eyes and 25 cataract eyes at the onset of surgery . miRNA next generation sequencing and bioinformatics analyses were performed using RNA extracted from 30 samples . The remaining 20 samples were used for quantitative polymerase chain reaction validation of sequencing results . A total of 341 microRNAs were detected in the aqueous humor samples of highly myopic eyes 201 miRNAs were detected in the aqueous humor samples of cataractous control eyes . A total of 249 mature miRNAs and 17 novel miRNAs were differentially expressed during myopia . Possible pathways regulated by these aberrantly expressed miRNAs included the TNF MAPK PI3K Akt and HIF 1 signaling pathways . The relative expression patterns of hsa let 7i 5p hsa miR 1273p and hsa miR 985p were confirmed by quantitative polymerase chain reaction . The current study provided an overall view of miRNA profiling in the aqueous humor of highly myopic eyes . These profiles may be associated with myopia pathogenesis and are potential biomarkers . | microRNA profiles in human eyes have not been reported. MiR 886 miR 369 miR 370 etc. were higher expressed in high myopia miR 10b miR 143 and miR 145 were suppressed. Aberrantly expressed miRNAs are crucial for precise diagnosis prognosis and response predictions of myopia. |
S0014483520302943 | Axonal transport blockade is an initial step in retinal ganglion cell degeneration in glaucoma and targeting maintenance of normal axonal transport could confer neuroprotection . We present an objective quantitative method for assessing axonal transport blockade in mouse glaucoma models . Intraocular pressure was elevated unilaterally in CD1 mice for 3 days using intracameral microbead injection . Longitudinal sections of optic nerve head were immunofluorescently labeled for myelin basic protein and amyloid precursor protein which is transported predominantly orthograde by neurons . The beginning of the myelin transition zone visualized with the MBP label was more posterior with elevated IOP 288.840.9m compared to normotensive control eyes 228.732.7m . Glaucomatous regional APP accumulations in retina prelaminar ONH unmyelinated ONH and myelinated optic nerve were identified by objective qualification of pixels with fluorescent intensity greater than the 97.5th percentile value of control eyes . This method segregated images with APP blockade from those with normal transport of APP . The fraction of suprathreshold pixels was significantly higher following IOP elevation than in normotensive controls in the unmyelinated ONH and myelinated nerve regions but not in retina or prelaminar ONH . The mean intensity of suprathreshold pixels was also significantly greater in glaucoma than in normotensive controls in prelaminar ONH unmyelinated ONH and myelinated optic nerve . Using this method subconjunctival glyceraldehyde which is known to worsen long term RGC loss with IOP elevation also produced greater APP blockade but not statistically significant compared to glaucoma alone . Systemic losartan which aids RGC axonal survival in glaucoma reduced APP blockade but not statistically significant compared to glaucoma alone . The method provides a short term assessment of axonal injury for use in initial tests of neuroprotective therapies that may beneficially affect RGC transport in animal models of glaucoma . | A method to quantify axonal transport blockade in mouse optic nerve is presented. Localized accumulation in four zones of the optic nerve was quantified. The method was applied to glaucoma pretreated with glyceraldehyde or losartan. Method can assess neuroprotection in glaucoma models at an early time point. |
S0014483520302955 | Our study aimed to investigate the differentially expressed circRNAs and their potential roles in orbital adipose connective tissue from patients with thyroid associated ophthalmopathy . The orbital adipose connective tissue samples from three TAO patients and three control individuals were collected for RNA sequencing after depletion of ribosomal RNA . Differentially expressed mRNAs and up regulated circRNAs were used for co expression analysis . Functional and pathway enrichment analysis were conducted for the up and down regulated mRNAs in the circRNA mRNA co expression network . Meanwhile circRNA miRNA interaction network was established by miRanda software . The expression levels of mRNAs and circRNAs in control and TAO samples were determined by qRT PCR . Among all the 16 329 circRNAs predicted from RNA sequencing data 163 circRNAs were differentially expressed in TAO samples . Besides 607 differentially expressed mRNAs were identified . The co expression analysis showed circRNA 14940 was correlated with CCND1 and TNXB while circRNA 10135 was correlated with PTGFR and circRNA 14936 was correlated with TNFRSF19 . The up regulated CCND1 participated in Wnt signaling pathway . The down regulated TNXB was involved in the ECM receptor interaction focal adhesion and PI3K Akt signaling pathway . PTGFR participated in neuroactive ligand receptor interaction and calcium signaling pathway . TNFRSF19 was involved in cytokine cytokine receptor interaction . In the interaction network circRNA 14936 could interact with hsa miR 103923p and circRNA 12367 could interact with hsa miR 12283p . Moreover the expression changes of MMP2 TNXB PTGFR CCND1 and TNFRSF19 as well as circRNA 14936 circRNA 14940 and circRNA 12367 were validated by qRT PCR . In conclusion the differentially expressed circRNAs might participate in pathogenesis of TAO and we speculated that circRNA 14940 CCND1 Wnt signaling pathway might be an important regulatory axis . | 607 mRNAs and 163 circRNAs were identified as differentially expressed in orbital adipose connective tissue of TAO. CircRNA mRNA co expression and circRNA miRNA interaction networks were constructed to reveal the roles of circRNAs in TAO. Expressions of MMP2 TNXB PTGFR CCND1 TNFRSF19 circRNA 14936 circRNA 14940 and circRNA 12367 were validated by qPCR. |
S0014483520302967 | Artificial cornea is an effective treatment option for cases of severe corneal loss . In this study we prepared a core skirt designed artificial cornea with orthogonal microfiber grid scaffold . We fabricated PCL orthogonal microfiber grid scaffolds by a direct writing technique and then combined them with compressed collagen to obtain a sandwich like CC P . PHEMA hydrogel and the CC P served as the core and the skirt respectively with the P also serving as an intermediate between the two . The physical properties of the artificial cornea including the morphology the mechanical properties and the light transmittance were evaluated . SEM images showed an effective connection and a lack of phase separation at the interface between the core and the skirt and the skirt formed a highly porous scaffold that promoted tissue biointegration . In addition we used the skirt structure to construct a corneal tissue model containing two cells types corneal stromal stem cells and mouse hippocampal neurons . The results showed that the cells could grow and differentiate well and the orthogonal microfiber grid scaffold fibers were good guides for the structural growth of CSSCs and neuronal axons . | Preparation of orthogonal microfiber grid scaffold by direct writing technology. A new core skirt artificial cornea in which microfiber grid scaffolds act as a connection between the core and the skirt. Constructed a 3D co culture model of corneal stromal cells and neurons. |
S0014483520302980 | Evidence suggests that the relevant variable in the anti myopigenic effect of increased time spent outdoors is the increase in light intensity . Because light is the strongest Zeitgeber it is plausible that the effects of bright light exposure depend on time of day and may impact circadian rhythms . In these studies we asked whether the effects on eye growth rates and ocular rhythms of brief daily exposures to bright light differed depending on time of day in eyes developing myopia in response to form deprivation or negative lens induced hyperopic defocus . We also studied the effects of concurrent exposures to brief hyperopic defocus and bright light . | Brief bright light inhibits myopic eye growth only when given in the evening. Concurrent brief bright light and hyperopic defocus inhibits growth in the morning. Bright light at transition times affect ocular rhythms. Effect of bright light on eye growth depend on whether defocus is continuous or brief. |
S0014483520302992 | Animal studies suggest that the retinal dysfunction in diabetic subjects that precedes overt clinical vasculopathy may be due to a retinal dopamine deficit . We analyzed levels of dopamine and its primary metabolite 3 4 dihydroxyphenylacetic acid in the vitreous of diabetic and non diabetic human subjects . Adult patients undergoing pars plana vitrectomy for non hemorrhagic indications were prospectively recruited from the Emory Eye Center in Atlanta GA. Vitreous samples were analyzed using high performance liquid chromatography to measure levels of DOPAC and DA in the vitreous specimens . Vitreous samples from 9 diabetic patients and 20 from non diabetic patients were analyzed . No eyes had apparent diabetic retinopathy . Mean normalized DA concentration in vitreous of diabetic subjects was 0.760.12pg L | Animal models of diabetes mellitus DM indicate that deficits in retinal dopamine precede vascular dysfunction and contribute to compromised visual function. Levels of dopamine and 3 4 dihydroxyphenylacetic acid DOPAC in vitreous of human subjects were analyzed. No statistically significant differences in dopamine or DOPAC levels were found between samples from type II DM subjects and non diabetic subjects. |
S0014483520303006 | The purpose of this study was to evaluate the optic nerve head lamina cribrosa retina and choroid in school age children using spectral domain optical coherence tomography and to assess these structural parameters in relation to age axial length and refractive error . Healthy children ages 11.152.62 years underwent cycloplegic autorefraction biometry and SD OCT imaging in both eyes . Images were analyzed using custom written programs in MATLAB after adjustment for lateral magnification . Peripapillary retinal nerve fiber layer thickness retinal and choroidal thicknesses Bruch s membrane opening area minimum rim width and anterior lamina cribrosa surface depth were determined and analyzed with age axial length and refraction . Results show that axial length increased and refractive error became more myopic with increasing age R | Bruch s membrane opening area is larger in myopic children compared to non myopic children. Minimum rim width and anterior lamina cribrosa surface depth are not associated with age axial length or refraction. Foveal retinal thickness is significantly associated with age. Once corrected for lateral magnification rNFL thickness does not demonstrate thinning with increasing axial length. Findings provide evidence that ocular structures undergo remodeling with normal eye growth and during myopia development. |
S001448352030302X | Selective pericyte loss the histological hallmark of early diabetic retinopathy enhances the breakdown of the blood retinal barrier in diabetes . However the role of pericytes on BRB alteration in diabetes and the signaling pathways involved in their effects are currently unknown . To understand the role of diabetes induced molecular alteration of pericytes we performed transcriptomic analysis of sorted retinal pericytes from mice model of diabetes . Retinal tissue from non diabetic and diabetic mouse eyes were used to isolate pericytes through fluorescent activated cell sorting using pericyte specific fluorescent antibodies PDGFRb APC . For RNA sequencing and qPCR analysis a cDNA library was generated using template switching oligo and the resulting libraries were sequenced using paired end Illumina sequencing . Molecular functional pathways were analyzed using differentially expressed genes . Differential expression analysis revealed 217 genes significantly upregulated and 495 genes downregulated in pericytes isolated from diabetic animals . These analyses revealed a core set of differentially expressed genes that could potentially contribute to the pericyte dysfunction in diabetes and highlighted the pattern of functional connectivity between key candidate genes and blood retinal barrier alteration mechanisms . The top up regulated gene list included Ext2 B3gat3 Gpc6 Pip5k1c and Pten and down regulated genes included Notch3 Xbp1 Gpc4 Atp1a2 and AKT3 . Out of these genes we further validated one of the down regulated genes Notch 3 and its role in BRB alteration in diabetic retinopathy . We confirmed the downregulation of Notch3 expression in human retinal pericytes exposed to Advanced Glycation End products treatment mimicking the chronic hyperglycemia effect . Exploration of pericyte conditioned media demonstrated that loss of NOTCH3 in pericyte led to increased permeability of endothelial cell monolayers . Collectively we identify a role for NOTCH3 in pericyte dysfunction in diabetes . Further validation of other DEGs to identify cell specific molecular change through whole transcriptomic approach in diabetic retina will provide novel insight into the pathogenesis of DR and novel therapeutic targets . | Transcriptomic analysis of pericytes isolated from diabetic animals revealed a core set of DEGs. The top up and down regulated genes may play a role in inflammation apoptosis pericyte migration and barrier alteration. Notch3 downregulation in diabetic pericytes may lead to increased autophagy inflammation and permeability changes as seen in DR. |
S0014483520303031 | Optic neuropathies such as glaucoma lead to retinal ganglion cell death . Transgenic mouse strains that express fluorescent proteins under the control of the Thy1 promoter have permitted single RGC imaging . Specifically in one strain of mice expressing yellow fluorescent protein fluorescence is expressed in only 0.2 of RGCs . This reduced expression allows visualization of the full dendritic arbour of YFP expressing RGCs facilitating the investigation of structural changes . As susceptibility amongst RGCs varies with morphology and subtype labelling methods should ideally non discriminately label RGCs to accurately determine the effects of experimental glaucoma . This study therefore sought to determine morphological subtypes of RGCs in the Thy1 YFP mouse strain . Retinas from Thy1 YFP mice were imaged | We identify 13 morphological clusters of retinal ganglion cells in Thy1 yellow fluorescent protein expressing mice. Among the 13 clusters there was a wide range in features with further variation within dendritic field size. Agreement with previous dye injection studies suggests Thy1 is expressed non discriminatingly in retinal ganglion cells. |
S0014483520303043 | The purpose of this study was to investigate whether single nucleotide polymorphisms of the tumor necrosis factor receptor superfamily and their ligand gene are associated with susceptibility to Behcet s Disease in Chinese Han . A two phase case control study was performed in 1055 BD patients and 1829 healthy controls . A total of 27 SNPs was tested using MassARRAY iPLEX technology . Data were analyzed using a Chi square test and Fisher s exact calibration test . The Bonferroni correction was applied for multiple testing . A statistically significant higher frequency of the A allele and a lower frequency of the G allele of rs1800692 was found in BD | We designed the population based two phase case control study. Identification of a novel SNP rs1800692 associated with BD in a Chinese Han population. The polymorphism of TNFRSF1A might confer genetic susceptibility to BD in a Chinese Han population. Our data provides a new insight into the role of TNF pathway in BD and may lead to novel treatments. |
S0014483520303055 | Segmental flow in the human trabecular meshwork is a well documented phenomenon but in depth mechanistic investigations of high flow and low flow regions are restricted due to the small amount of tissue available from a single donor . To address this issue we have generated and characterized multiple paired HF and LF cell strains . Here paired HF and LF cell strains were generated from single donors . Cells were characterized for growth and proliferation as well as gene and protein expression of potential segmental region markers . Cells isolated from HF and LF regions have similar growth and proliferation rates . Gene expression data reveals vascular cell adhesion protein 1 thrombospondin 2 and tissue inhibitor of metalloproteinase 1 are potential markers of LF cells | Here we generate novel cell strains from segmental regions of human TM tissues. High flow and low flow cell strains have similar growth and proliferation rates. THBS2 VCAM1 and TIMP1 are potential low flow cell markers. Low flow cell markers may be useful for developing targeted therapeutics. |
S0014483520303067 | Epithelial to mesenchymal transition contributes to fibrosis associated pathologies including scarring of different ocular tissues . Recently targeting EMT is seen as an appropriate therapeutic approach for different fibrosis related eye diseases such as macular degeneration or glaucoma surgery related fibrosis . Nevertheless for ocular surface diseases target genes specific for particular cell type or condition are still undefined . This study aimed to expose the complex regulatory mechanisms that trigger EMT in human conjunctival epithelial cells . EMT was induced by prolonged treatment with two TGF isoforms TGF 1 and TGF 2 and their combination . TGF 1 showed the strongest potential for initiating EMT in HCjE cells reflected on morphological changes cell migration and the levels of mRNA expression of different epithelial | HCjE cells are prone to EMT triggered by prolonged TGF 1 but not TGF 2 treatment. The DNA demethylation agent 5 AzaC reverts EMT in TGF 1 treated HCjE cells. miRNAs are the main targets of 5 AzaC in TGF 1 treated HCjE cells. DNA methylation of the miR 200 family is the key step in EMT induction in HCjE cells. miR 200 loci are candidates for epigenetic treatment in EMT based eye diseases. |
S0014483520303080 | The purpose of this study is to evaluate outflow pathways from subconjunctival blebs and to identify their identity . Post mortem porcine human and bovine eyes were acquired and tracers were injected into the subconjunctival space to create raised blebs where outflow pathways were visualized qualitatively and quantitatively . Rodents with fluorescent reporter transgenes were imaged for structural comparison . Concurrent optical coherence tomography was obtained to study the structural nature of these pathways . Using fixable fluorescent dextrans tracers were trapped to the bleb outflow pathway lumen walls for histological visualization and molecular identification using immunofluorescence against lymphatic and blood vessel markers . Bleb outflow pathways could be observed using all tracers in all species . Quantitative analysis showed that the nasal quadrant had more bleb related outflow pathways compared to the temporal quadrant nasal 1.90.3 pathways vs. temporal 0.70.2 pathways | Glaucoma bleb forming surgeries rely upon subconjunctival aqueous outflow. Subconjunctival drug delivery is limited by subconjunctival aqueous outflow. Subconjunctival outflow is hypothesized to be via lymphatics or blood vessels. Structural molecular imaging demonstrates use of the lymphatic route. Better understood enhancing minimizing lymphatic outflow may benefit eye care. |
S001448352030316X | Recently we discovered that the cosmetic preservatives benzalkonium chloride and formaldehyde are especially toxic to human meibomian gland epithelial cells . Exposure to these agents at concentrations approved for human use leads within hours to cellular atrophy and death . We hypothesize that these effects are not unique and that other cosmetic preservatives also exert adverse effects on HMGECs . Such compounds include parabens phenoxyethanol and chlorphenesin which have been reported to be toxic to corneal and conjunctival epithelial cells the liver and kidney as well as to irritate the eye . To test our hypothesis we examined the influence of parabens phenoxyethanol and chlorphenesin on the morphology signaling survival proliferation and lipid expression of immortalized HMGECs . These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben ethylparaben phenoxyethanol and chlorphenesin for up to 5 days . We monitored the signaling ability appearance number and neutral lipid content of the IHMGECs as well as their lysosome accumulation . Our findings show that a 30 min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway . This effect is dose dependent and occurs at concentrations equal to and less than those dosages approved for human use . Further a 24 h treatment of the IHMGECs with concentrations of methylparaben ethylparaben phenoxyethanol and chlorphenesin close to or at the approved human dose induces cellular atrophy and death . At all concentrations tested no preservative stimulated IHMGEC proliferation . Of particular interest it was not possible to evaluate the influence of these preservatives at close to human approved dosages on IHMGEC differentiation because the cells did not survive the treatment . In summary our results support our hypothesis and show that methylparaben ethylparaben phenoxyethanol and chlorphenesin are toxic to IHMGECs . | At concentrations approved for human use we measured the effect of cosmetic preservatives methylparaben ethylparaben phenoxyethanol and chlorphenesin on the morphology signaling ability survival proliferation and differentiation of IHMGECs. Our findings support our hypothesis and show that the cosmetic preservatives methylparaben ethylparaben phenoxyethanol and chlorphenesin are toxic to IHMGECs. |
S0014483520303171 | Dry eye syndrome is a common disease associated to eyes inflammation irritation and tear film instability . The enzymatic complex of xanthine oxidoreductase is involved in the generation of reactive oxygen species and uric acid that in the end can cause reperfusion injuries irritation and pathological conditions . Furthermore in the eye it has been proposed that oxygen free radicals might play a significant role in retinal ischemic damage . | Arabinogalactan AG and hyaluronic acid HA artificial drops AD was studied. AG entails uric acid UA and ROS reduction of 27 and 38 . HA involves no statically significant reduction of uric acid or ROS. AG and HA combination involves the reduction of UA and ROS equal to 38 and 62 . |
S0014483520303183 | Structure and function of the retina mainly rely on its fatty acid composition . Evidence from epidemiological studies and from animal experiments indicates that FA composition of the retina is influenced by the diet . Mice under chronic high fat diet develop metabolic syndrome a risk factor for diabetes that is associated with structural and functional alterations of the retina . Here we studied the impact of chronic exposure of mice to HFD on retinal FA composition . | HFD modifies the relative proportion of retinal linoleic and alpha linolenic acids. Imbalance in retinal essential fatty acids had no impact on the DHA and AA content. HFD decreases retinal omega 7 MUFAs. HFD modulates retinal content in plasmalogens. |
S0014483520303195 | Leucine rich 2 glycoprotein 1 is involved in several pathophysiological processes including angiogenesis cutaneous wound repair and cancer metastasis . In this study we investigated the potential role and mechanism of LRG1 in corneal re epithelialisation and nerve regeneration in streptozotocin induced diabetic mice . We found decreased levels of LRG1 in the corneal epithelium after wounding in diabetic mice compared to normal controls . Hyperglycaemia downregulated the LRG1 expression in the corneal epithelium in vivo | Hyperglycemia downregulated the expression of Leucine rich 2 glycoprotein 1 LRG1 in corneal epithelial cells. LRG1 accelerated corneal epithelial wound healing and nerve regeneration both in normal and diabetic mice. LRG1 accelerated corneal re epithelialisation and nerve regeneration via upregulation of matrix metalloproteinase MMP 3 and MMP13. LRG1 interacted with MMP3 and MMP13. |
S0014483520303201 | The objective of this study is to characterize the retinal degeneration phenotype of CXCR5 NRF2 double knockout mice at the early adult age . CXCR5 KO mice and NRF2 KO mice were bred to create CXCR5 NRF2 DKO mice . The assessment of RD features included fundus and optical coherence tomography imaging periodic acid Schiff and immunofluorescence staining of retinal pigment epithelium choroid flatmounts . Stained samples were imaged with fluorescent microscopy and Western blots were used to monitor protein expression changes . The staining of cleaved caspase 3 and PNA lectin was performed to assess the presence of photoreceptor cell apoptosis . Quantification and statistical analyses were performed with Image J and Graphpad software . The young adult DKO mice exhibited increased hypopigmented spots on fundus and sub RPE abnormalities on OCT as compared to the CXCR5 KO mice and C57BL6 WT controls . PAS stained sections demonstrated aberrant RPE sub RPE depositions . The DKO mice had increased sub RPE depositions of IgG and AMD associated proteins . The protein expression of AMD associated proteins and microglia marker were upregulated at the RPE BM choroid complex of DKO mice . The adult DKO mice underwent photoreceptor cell apoptosis compared to the single CXCR5 and NRF2 KO and the WT mice at an early adult age . Mechanistically increased expression of CXCL13 and N cadherin was observed as a sign of epithelial mesenchymal transition . The data suggest that the CXCR5 NRF2 DKO mice develop RD characteristics at an early age and may serve as a valuable animal model of RD . | CXCR5. and NRF2. mice are known to develop retinal degeneration with age. Both strains were cross bred to create CXCR5. .NRF2. double knockout DKO mice. DKO mice develop retinal degeneration at early adult age 46 months . DKO mice have increased microglia marker TMEM119 and accumulation of IgG in RPE and retina. DKO mice demonstrate the accumulation of AMD associated proteins amyloid Apolipoprotein E B crystallin in sub RPE. |
S0014483520303213 | The study of corneal stromal keratocytes is motivated by its strong association with corneal health and visual function . They play a dominant role in the maintenance of corneal homeostasis and transparency through the production of collagens proteoglycans and corneal crystallins . Trauma induced apoptosis of keratocytes and replacement by fibroblasts and myofibroblasts disrupt the stromal matrix organization resulting in corneal haze formation and vision loss . It is therefore important to understand the biology and behaviours of keratocytes and the associated stromal cell types in wound healing corneal pathologies as well as different ophthalmic situations . The recent development of | Corneal stromal keratocytes have strong link to corneal health and visual functions. Keratocyte changes alter stromal organization causing opacities and vision loss. Important to study their roles in ocular pathologies wound healing and treatments. Progress of cell and or scaffold based approach in stromal regeneration. |
S0014483520303225 | Limbal epithelial stem cells are required for the maintenance and repair of the corneal epithelial surface . The difficulty in obtaining human corneal tissue for research purposes means that animal models for studying the corneal and limbal epithelium are extremely useful . Porcine corneal tissue represents an attractive experimental model however functional analysis of the limbal epithelial cell population is needed to validate the use of this tissue . Single cell clonal analysis revealed that holoclone generating cells were enriched in the limbus as compared with the central cornea and that label retaining cells were also enriched in the limbus and compared with the central cornea . Furthermore it was demonstrated that in a 3D printed organ culture system porcine tissue was capable of maintaining and healing the corneal epithelium . Ki67 staining of corneal sections revealed that in response to central epithelial wounding a greater proportion of progenitors in the basal limbal epithelium enter an actively dividing state . The authors present a comprehensively validated model system for studying the interactions between limbal niche factors and limbal epithelial stem cell fate . | Stem cells are enriched in the porcine limbus and this represents a suitable model for studying the human limbus. Organ cultured porcine corneas with an intact limbus are capable of maintaining the corneal epitehlium. The proliferative response of limbal epitehlial progenitors to wounding can be visualised |
S0014483520303237 | This work sought to compare aqueous angiographic segmental patterns with bead based methods which directly visualize segmental trabecular meshwork tracer trapping . Additionally segmental protein expression differences between aqueous angiographic derived low and high outflow human TM regions were evaluated . Post mortem human eyes were perfused with fluorescent tracers indocyanine green and or fluorescent microspheres . After angiographic imaging peri limbal low and high angiographic flow regions were marked . Aqueous angiographic segmental outflow patterns were similar to fluorescent microsphere TM trapping segmental patterns . TM was dissected from low and high flow areas and processed for immunofluorescence or Western blot and compared . Versican expression was relatively elevated in low flow regions while MMP3 and collagen VI were relatively elevated in high flow regions . TGF 2 thrombospondin 1 TGF receptor1 and TGF downstream proteins such as smooth muscle actin were relatively elevated in low flow regions . Additionally fibronectin levels were unchanged but the EDA isoform that is associated with fibrosis was relatively elevated in low flow regions . These results show that segmental aqueous angiographic patterns are reflective of underlying TM molecular characteristics and demonstrate increased pro fibrotic activation in low flow regions . Thus we provide evidence that aqueous angiography outflow visualization the only tracer outflow imaging method available to clinicians is in part representative of TM biology . | Aqueous Angiography AA is capable of visualizing segmental aqueous humor outflow AHO in living human eyes. AA segmental AHO patterns matched that of bead based methods which trapper tracers in the trabecular meshwork TM . AA determined high and low flow TM regions showed segmental changes in pro fibrotic markers. |
S0014483520303249 | Diabetic retinopathy is a neurovascular complication of diabetes mellitus that leads to blindness in the working age population . Retinal Mller cells proliferate and produce pro angiogenic factors including vascular endothelial growth factor and hepatocyte growth factor via the reactive oxygen species thioredoxin interacting protein NACHT LRR and PYD domain containing protein 3 inflammasome axis to promote proliferative DR. Epigallocatechin 3 gallate plays anti oxidant anti inflammatory anti proliferative and anti angiogenic roles in Mller cells . A prodrug of EGCG enhances the bioavailability of EGCG . In an in vitro model of high glucose stimulated Mller cells pro EGCG inhibited proliferation and pro angiogenic factor production by down regulating the activity of the ROS TXNIP NLRP3 inflammasome axis . In a mouse DR model pro EGCG reduced ROS accumulation NLRP3 inflammasome activation Mller cell proliferation and production of the pro angiogenic factors VEGF and HGF . In summary pro EGCG mitigated hyperglycaemia challenged Mller cell proliferation and pro angiogenic factor production by inhibiting ROS TXNIP NLRP3 inflammasome signalling implying a potential therapeutic strategy for DR . | Mller cells proliferate and produce pro angiogenic factors including vascular endothelial growth factor VEGF and hepatocyte growth factor HGF via the reactive oxygen species ROS thioredoxin interacting protein TXNIP NACHT LRR and PYD domains containing protein 3 NLRP3 inflammasome axis to promote proliferative DR. In an in vitro model of high glucose stimulated Mller cells pro EGCG inhibited proliferation and pro angiogenic factor production by downregulating ROS TXNIP NLRP3 inflammasome axis activity. In a mouse DR model pro EGCG reduced ROS accumulation NLRP3 inflammasome activation Mller cell proliferation and production of the pro angiogenic factors VEGF and HGF. Pro EGCG mitigated hyperglycaemia challenged Mller cell proliferation and pro angiogenic factor production by inhibiting ROS TXNIP NLRP3 inflammasome signalling. |
S0014483520303250 | In this work we have analyzed the main clinical and corneal histological parameters that may be associated to the spherical equivalent age and gender of individuals with myopic refractive errors . For this purpose 108 cornea stroma lenticules were obtained from patients subjected to ReLEx SMILE myopia correction . Histological analyses were carried out and histochemistry and immunohistochemistry were used to quantify key histological components of the cornea stroma including mature collagen fibers reticular and elastic fibers glycoproteins proteoglycans type V collagen and several crystallins . Clinical and histological data were analyzed to determine their association with SE age and gender . Results showed a significant correlation between the age range of the patients and the expression of crystallins CRY A CRY 1 and type V collagen and between CRY 1 and corneal thickness spherical diopters and SE although correlation between CRY 1 and SE was non significant when age was controlled . Comparison of cases with low myopia and high moderate myopia found statistical differences for D and lenticule thickness and diameter . The binary logistic regression analysis allowed us to construct a model using two clinical parameters . Parameters showing significant correlation with the age were the corneal radius keratometry reading OZ CRY A and type V collagen whereas SE lenticule thickness OZ CRY 1 and type V collagen showed statistically significant differences between the youngest and the oldest patients . A binary logistic regression analysis model was generated including 3 variables . No gender differences were found . The specific clinical and histological modifications found to be associated to the SE and age could be useful for a better understanding of the mechanisms involved in the genesis or progression of myopia and could establish the basement for future therapeutic options . | High myopia is associated to the expression of CRY 1 by the cornea stroma. The age of the patient is associated to CRY A CRY 1 and type V collagen. No correlation between high myopia and gender was found. |
S0014483520303274 | The mammalian cornea maintains its thickness and transparency primarily by the activity of a fluid pump located in the endothelial cell layer . The accepted concept the pump leak theory holds that the active transport of solute from the stroma to the aqueous humor leads to a steady state osmotic pressure gradient across the endothelium that balances the imbibition pressure created by the hydrophilic proteoglycans in the stromal ground substance . The details of this process are controversial and some of the classical in vitro studies aimed to explore the fluid pump using low temperature to challenge the regulatory behavior can not be duplicated in vivo . The activity of sensory or sympathetic innervation may play a role in this low temperature tolerance . Asymmetry in endothelial cell volume regulation could be the basis for the fluid pump . | The pump leak theory for the corneal endothelial control of corneal hydration although decades old is still valid. This theory holds that the transport of solute creates an osmotic gradient to balance the stromal swelling pressure. The associated term fluid pump is a misnomer in that steady state fluid flow is a consequence of the solute transport. Sensory and or sympathetic corneal innervation may play a role in the regulatory process. Asymmetry in endothelial cell volume regulation could be the basis for the fluid pump. |
S0014483520303286 | Uveal melanoma is the most common primary intraocular malignancy in adults and has a high mortality rate . Tumor microenvironment is crucial in controlling and influencing the behavior of malignant tumors . Thus illustrating the prognostic values of adaptive immune resistance signatures and infiltrating immune cells in the TME of UM may provide scientific rationales for immunotherapy . In this study the gene expression data of 80 primary UM and 103 primary skin cutaneous melanoma samples with relevant clinical information were obtained from The Cancer Genome Atlas database . The TME was analyzed by the xCell EPIC ESTIMATE and TIMER algorithms . The relationships and prognostic values of immune infiltrates and mutated genes were further investigated . We found that primary UM and primary SKCM exhibited distinct TMEs . Higher levels of infiltrating stromal and immune cells in UM were related to more aggressive biology and poor prognosis . Increased CD8 | Primary UM and primary SKCM exhibit distinct TMEs. Higher levels of infiltrating stromal and immune cells in UM are related to more aggressive biology and poor prognosis. Increased levels of CD8. T cells and adaptive immune resistance markers are predictive factors for poor prognosis in UM. Some common mutations in UM are associated with its TME. |
S0014483520303298 | Vogt Koyanagi Harada disease is a common type of uveitis in China but the diagnosis criteria of VKH disease is controversial . The aim of this study was to investigate potential diagnostic plasma biomarkers for VKH disease . A case control study including 55 VKH patients and 30 healthy controls in a tertiary referral center was performed . The metabolic phenotype of VKH patients showed a significant difference compared to healthy controls . Fifteen differentially expressed metabolites were identified between active VKH patients and healthy controls and nine DEMs were found between inactive VKH patients and healthy controls after controlling variable importance in the projection value 1 and false discovery rate 0.05 . D mannose stearic acid and L lysine were shown to be potential diagnostic biomarkers which can discriminate active VKH patients from healthy controls with a diagnostic performance with AUC 0.965 0.936 and 0.910 respectively in independent diagnosis and an AUC 0.999 when combined . Sarcosine was recognized as an independent potential biomarker which could distinguish inactive VKH patients from healthy controls . This study reveals a significant difference of plasma metabolic phenotype and identifies diagnostic biomarkers for VKH disease . Changes in the metabolic profile may provide clues towards the pathophysiology of VKH disease . | A plasma metabolomics study of VKH disease is presented. A different plasma metabolic phenotype disease was found in VKH disease. D mannose L lysine and stearic acid can be potential diagnostic biomarkers. |
S0014483520303304 | Bone marrow mesenchymal stem cell derived small extracellular vesicles but not fibroblast sEV provide retinal ganglion cell neuroprotection both | Damage to the optic nerve leads to permanent loss of retinal ganglion cells RGC . Neuroprotective strategies are required to prevent loss of RGC and function. The ability of miRNA to down regulate mRNA makes them a candidate treatment. Here we deliver multiple miRNA to retinae of animals prior to optic nerve crush. Combinations of miRNA are able to prevent RGC loss and preserve their function. |
S001448352030333X | Limbal function is a key determinant of corneal epithelial integrity . Lineage tracing studies in mice have highlighted that the centripetal movement of epithelial progenitors from the limbus drives both the steady state maintenance of the corneal epithelium and its regeneration following injury . It is well established that this is facilitated by a population of limbal epithelial stem cells within the limbus . It is becoming increasingly apparent that the behaviour of these stem cells and their ability to respond to the needs of the tissue are closely linked to their immediate microenvironment the stem cell niche . Increasing understanding of the structural features of this niche and the signalling networks that they coordinate is required to enhance the therapeutic application of these cells in the treatment of limbal stem cell deficiency . Importantly an improved characterisation of the hierarchy of limbal epithelial progenitors using both new and old putative markers will enable a greater appreciation for the effects of many of these limbal niche factors on stem cell fate . | Corneal epithelial cells are primarily derived from cells originating in the limbal epithelium. Niche integrity is required for repopulation of the limbus with progenitors following selective removal of limbal epithelium. The canonical Wnt catenin signalling pathway is a key regulator of stem cell characteristics of the LESCs. The relatively reduced stiffness of limbal tissue represents a novel niche factor in the regulation of LESC fate. Rather than representing a single population of cells LESCs may exist in separate but cooperative subpopulations. |
S0014483520303353 | The aim of this study was to examine the expression of the cytokines and chemokines receptor 3 molecule in endothelial cells and vascular structures in a murine model of corneal neovascularization and in samples of neovascularized human corneas . An immunofluorescence assay using the murine model showed a greater proportion and intensity of CCR3 in the epithelium and corneal subepithelial regions in corneas with neovascularization . In the absence of vascularization no CCR3 was found . Of the 32 studied tissues eight were vascularized and 24 were avascular . In the human corneas vascularized corneas showed positive labeling for CD31 in all the analzedtissues as well as positive labeling for CCR3 . Therefore all vascularized tissues showed positive coexpression of CCR3 and CD31 whereas none of the avascular corneas showed immunolabeling for either of these receptors . These results suggest that CCR3 could be a possible marker for corneal neovascularization with potential to be a therapeutic target . | CCR3 receptor is present in vascularized corneal tissue. There is a CCR3 CD31 colocalization in corneal neovessels. There is discrete expression of eotaxin3 in neovascularized corneas. |
S0014483520303365 | We reviewed the literature on the aqueous humor proteome of primary open angle glaucoma patients in order to obtain deeper insight into the pathophysiology of POAG . We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG and cataract . Untargeted studies were divided into two subgroups depending on the type of surgery during which POAG AH was collected glaucoma filtration surgery or cataract surgery . We reanalyzed the raw data or combined the reported data to perform GO enrichment and pathway analysis . Out of 93 eligible proteomic studies seven were untargeted studies that identified 863 AH proteins . We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2 . Both subgroups were characterized by activation of the acute immune response dysregulation of folate metabolism and dysregulation of the selenium micronutrient network . For subgroup 1 but not for subgroup 2 proteins of the complement system were significantly enriched . AH proteome of POAG patients shows strong activation of the immune system . In addition analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors . In view of their glaucoma surgery POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG . The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression . | Reanalyzed or combined outcome of untargeted proteomic studies LC MS MS on glaucoma aqueous humor. The immune system is activated in glaucoma aqueous humor. There is dysregulation of selenium and folate in glaucoma aqueous humor. Aqueous humor proteome differs between progressive filtration surgery and stable cataract surgery glaucoma patients. The complement system is strongly dysregulated in the aqueous humor of progressive glaucoma patients. |
S0014483520303377 | Scleritis is a sight threatening inflammation characterized by severe pain and redness of the eye . It can cause blindness by severe complications like scleral and corneal necrosis keratitis and uveitis . The pathogenesis of scleritis is largely unknown due to a combination of the rarity of the disease the little available human tissue based research material and the lack of animal models . The immune system is assumed to play a crucial role in the pathogenesis of scleritis . Multiple clues indicate probable antigenic stimuli in scleritis and the involvement of matrix metalloproteinases in the destruction of scleral tissue . In this article we review the current insights into the pathogenesis of scleritis and we suggest new hypotheses by implementing knowledge of systemic autoimmune disease pathogenesis . Understanding the pathogenesis of scleritis is crucial to improve the clinical management as well as to find novel treatment modalities . | The pathogenesis of scleritis a sight threatening ocular inflammation characterized by intense pain is largely unknown. Autoimmunity has been hypothesized however defining autoantibodies and or T cell reactivity are not yet clarified. Matrix metalloproteinases may be responsible for scleral destruction their blockage may enrich current treatment options. Rapidly evolving imaging techniques can provide additional insight in the pathogenesis of scleritis. |
S001448352030347X | The effect of various combinations of cervical arterial ligations on retinal blood flow levels is not known in rats . We hypothesized 1 No artery exists between the Circle of Willis and the eye 2 Selective Combinations enable varying RBF levels between normal and zero 3 In certain Combinations the capillary bed of the head participates in supplying the eye . Twenty six Combinations were studied in one eye of 20 Long Evans rats under general anesthesia . RBF was quantitatively evaluated with our published imaging methods based on direct measurements of venous diameter and blood velocity from the displacement of fluorescent microspheres over time . For each Combination one or more RBF values were measured . Data were obtained from 59 runs . Levels of RBF ranged from normal to zero . An artery between the Circle of Willis and the eye was excluded . With some Combinations flow traversed the capillary bed . Combinations were consolidated into five Groups based on the blood flow paths remaining after the ligations . A mixed linear model accounting for multiple measurements in the same eye demonstrated an effect of Group on RBF . By major source of ocular blood supply the trend of RBF levels was ipsilateral carotid artery contralateral carotid artery ipsilateral distal internal carotid artery retrograde from Circle of Willis . The findings advanced knowledge of the sources of blood supply to the rat eye and demonstrated a method of selective cervical arterial ligations for varying RBF levels with potential to impact future retinal ischemia research . | Various combinations of cervical ligations can clarify blood supply to the eye. There is no direct communication between the Circle of Willis and the eye. The pterygopalatine artery is the input to the ophthalmic artery. The capillary bed of the head can be a link in the ocular blood supply. By choosing the ligations retinal blood flow can be varied from normal to zero. |
S0014483520303481 | The corneal wound healing response is typically initiated by injuries to the epithelium and or endothelium that may also involve the stroma . However it can also be triggered by immune or infectious processes that enter the stroma via the limbal blood vessels . For mild injuries or infections such as epithelial abrasions or mild controlled microbial infections limited keratocyte apoptosis occurs and the epithelium or endothelium regenerates the epithelial basement membrane and or Descemet s basement membrane is repaired and keratocyte or fibrocyte derived myofibroblast precursors either undergo apoptosis or revert to the parent cell types . For more severe injuries with extensive damage to EBM and or DBM delayed regeneration of the basement membranes leads to ongoing penetration of the pro fibrotic cytokines transforming growth factor 1 TGF2 and platelet derived growth factor that drive the development of mature alpha smooth muscle actin myofibroblasts that secrete large amounts of disordered extracellular matrix components to produce scarring stromal fibrosis . Fibrosis is dynamic with ongoing mitosis and development of SMA myofibroblasts and continued autocrine or paracrine interleukin 1 mediated apoptosis of myofibroblasts and their precursors . Eventual repair of the EBM and or DBM can lead to at least partial resolution of scarring fibrosis . | Keratocyte apoptosis is the first observable stromal event after anterior corneal injury. Normal or defective regeneration of the EBM controls regenerative vs. fibrotic healing. Descemet s membrane modulates regenerative vs. fibrotic healing for posterior injuries. Fibrosis is dynamic with ongoing mitosis development and apoptosis of myofibroblasts. |
S0014483520303493 | Basement membranes are layers of extracellular matrix which anchor the epithelium or endothelium to connective tissues in most organs . Descemet s membrane which is the basement membrane for the corneal endothelium is a dense thick relatively transparent and cell free matrix that separates the posterior corneal stroma from the underlying endothelium . It was historically named Descemet s membrane after Jean Descemet a French physician but it is also known as the posterior limiting elastic lamina lamina elastica posterior and membrane of Demours . Normal Descemet s membrane ultrastructure in humans has been shown to consist of an interfacial matrix that attaches to the overlying corneal stroma an anterior banded layer and a posterior non banded layerupon which corneal endothelial cells attach . These layers have been shown to have unique composition and morphology and to contribute to corneal homeostasis and clarity participate in the control of corneal hydration and to modulate TGF induced posterior corneal fibrosis . Pathophysiological alterations of Descemet s membrane are noted in ocular diseases such as Fuchs dystrophy bullous keratopathy keratoconus primary congenital glaucoma as well as in systemic conditions . Unrepaired extensive damage to Descemet s membrane results in severe corneal opacity and vision loss due to stromal fibrosis which may require penetrating keratoplasty to restore corneal transparency . The purpose of this article is to highlight the current understanding of Descemet s membrane structure function and potential for regeneration . | Descemet s membrane is the basement membrane of the corneal endothelium. Descemet s membrane modulates aqueous humor TGF beta and stromal fibrosis. Descemet s membrane has poor potential to regenerate. |
S001448352030350X | Physico chemical properties of three cataract associated missense mutants of B crystallin were analyzed . The oligomers formed by the R11H mutant were smaller whereas the oligomers of the P20S and R56W mutants were larger than those of the wild type protein . The P20S mutant possessed lower thermal stability than the wild type HspB5 or two other HspB5 mutants . All HspB5 mutants were able to form heterooligomeric complexes with A crystallin a genuine component of eye lens . However the P20S and R56W mutants were less effective in the formation of these complexes and properties of heterooligomeric complexes formed by these mutants and HspB4 and analyzed by ion exchange chromatography were different from those formed by the wild type HspB5 and HspB4 . All HspB5 variants also heterooligomerized with another partner protein HspB6 . Specifically for the P20S mutant forming two distinct sizes of homooligomers only the smaller homooligomer population was able to interact with HspB6 . P20S and R56W mutants possessed lower chaperone like activity than the wild type HspB5 when UV irradiated | Cataract associated R11H P20S R56W mutants of B crystallin HspB5 were analyzed. Mutation R11H decreases while P20S and R56W increase the size of HspB5 oligomers. All mutations affect the interaction of HspB5 with its genuine partner HspB4. P20S mutant has lower chaperone like activity in vitro than the wild type protein. Effect of mutations correlates with their putative location in helical regions. |
S0014483520303535 | The anterior surface of the eye functions as a barrier to the external environment and protects the delicate underlying tissues from injury . Central to this protection are the corneal limbal and conjunctival epithelia . The corneal epithelium is a self renewing stratified squamous epithelium that protects the underlying delicate structures of the eye supports a tear film and maintains transparency so that light can be transmitted to the interior of the eye . In this review dedicated to James Funderburgh and his contributions to visual science in particular the limbal niche corneal stroma and corneal stromal stem cells we will focus on recent data on the identification of novel regulators in corneal epithelial cell biology their roles in stem cell homeostasis wound healing limbal corneal boundary maintenance and the utility of single cell RNA sequencing in vision biology studies . | Limbal corneal epithelial stem cell biology. Application of single cell RNAseq to limbal epithelial stem cells. The role of autophagy in stem cell maintenance. How microRNAs contribute to limbal epithelial stem cell homeostasis. Eph ephrins help to regulate the limbal corneal epithelial boundary. |
S0014483520303614 | Primary blast injury to the retina and optic nerve causes progressive visual loss and neurodegeneration . Military personnel are exposed to multiple low overpressure blast waves which may be in quick succession such as during breacher training or in combat . We investigated the necroptotic cell death pathway in the retina in a mouse repeated primary ocular blast injury model using immunohistochemistry . We further evaluated whether intravitreal injections of a potent necroptosis inhibitor Necrostatin 1s protects the retina and ON axons by retinal ganglion cells counts ON axonal counting and optical coherence tomography analysis of vitreous haze . Receptor interacting protein kinase 3 increased in the inner plexiform layer 2 days post injury and persisted until 14 dpi whilst RIPK1 protein expression did not change after injury . The number of degenerating ON axons was increased at 28 dpi but there was no evidence of a reduction in the number of intact ON axons or RNA binding protein with multiple splicing | The retina and optic nerve can be injured after repeated primary blast injury rPBI . Retinal necroptosis protein RIPK3 increased after rPBI. Intravitreal injections and rPBI can cause additive injury with increased cell death and inflammation. Treatment with pharmacological necroptosis inhibitor Necrostatin 1s may provide some retinal ganglion cell neuroprotection. |
S0014483520303626 | The lamina cribrosa is the initial site of glaucomatous injury . Pathological changes to the lamina cribrosa include posterior displacement of the lamina cribrosa loss of trophic support and remodeling of the extracellular matrix . Optic nerve head astrocytes and lamina cribrosa cells synthesize extracellular matrix proteins to support and maintain the lamina cribrosa under physiological conditions . During glaucoma these cells respond to mechanical strain and other stimuli which leads to pathological remodeling of the ONH . Although ONH astrocytes and lamina cribrosa cells have been previously cultured there is no well accepted straightforward technique to isolate both cell types from a single dissected human ONH . To better understand the pathophysiology of glaucoma we obtained and cultured lamina cribrosa explants from human donor eyes . Initially cells that grew out from the explant were ONH astrocytes and lamina cribrosa cells . Using a specialized medium we isolated pure populations of lamina cribrosa cells and ONH astrocytes . ONH astrocytes expressed glial fibrillary acidic protein . Lamina cribrosa cells expressed alpha smooth muscle actin but were negative for GFAP . This method of ONH cell isolation and cell culture will provide a technique to better understand the molecular and cell specific changes in glaucomatous damage to the ONH . | Dissection of human optic nerve head ONH . A technique to isolate human ONH astrocytes and lamina cribrosa cells from a single ONH explant. Characterization of ONH cells. |
S001448352030364X | Herein partially summarizes one scientist clinician s wanderings through the jungles of primate aqueous humor outflow over the past 45 years . Totally removing the iris has no effect on outflow facility or its response to pilocarpine whereas disinserting the ciliary muscle from the scleral spur trabecular meshwork completely abolishes pilocarpine s effect . Epinephrine increases facility in CM disinserted eyes . Cytochalasins and latrunculins increase outflow facility subthreshold doses of cytochalasins and epinephrine given together increase facility and phalloidin which has no effect on facility partially blocks the effect of both cytochalasins and epinephrine . H 7 ML7 Y27632 and nitric oxide donating compounds all increase facility consistent with a mechanosensitive TM SC . Adenosine A1 agonists increase and angiotensin II decrease facility . OCT and optical imaging techniques now permit visualization and digital recording of the distal outflow pathways in real time . Prostaglandin F2 analogues increase the synthesis and release of matrix metalloproteinases by the CM cells causing remodeling and thinning of the interbundle extracellular matrix thereby increasing uveoscleral outflow and reducing IOP . Combination molecules and fixed combination products simplify drug regimens for patients . Gene and stem cell therapies to enhance aqueous outflow have been successful in laboratory models and may fill an unmet need in terms of patient compliance taking the patient out of the delivery system . Functional transfer of genes inhibiting the rho cascade or decoupling actin from myosin increase facility while genes preferentially expressed in the glaucomatous TM decrease facility . In live NHP reporter genes are expressed for 2 years in the TM after a single intracameral injection with no adverse reaction . However except for one recent report injection of facility effective genes in monkey organ cultured anterior segments have no effect in live NHP . While intracameral injection of an FIV . BOVPGFS myc.GFP PGF synthase vector construct reproducibly induces an 2mmHg reduction in IOP the effect is much less than that of topical PGF | Cholinomimetics increase outflow facility solely via CM contraction. Epinephrine RKIs and NO facility by inhibiting TM contractility relaxing TM and dilating SC. PGF. Fu by CM cell MMP synthesis release and remodeling CM ECM collagen. Viral vectors can transfer reporter genes expressing for 2yrs in live monkey TM genes inhibiting TM contractility and facility in MOCAS and genes that facility in MOCAS perhaps presaging molecular models for human POAG. iPSC cell derived TM cells populated TM rescued outflow in several models. |
S0014483520303663 | Pathological ocular angiogenesis commonly results in visual impairment or even blindness . Unveiling the mechanisms of pathological angiogenesis is critical to identify the regulators and develop effective targeted therapies . Here we used corneal neovascularization model to investigate the mechanism of pathological ocular angiogenesis . We show that | We used cornea as a unique system for studying the mechanism of pathological ocular angiogenesis. FTO regulates the progression of corneal neovascularization. FTO regulates vascular endothelial function via m. A YTHDF2 mechanism. Targeting m. A modification is a potential therapy for pathological ocular angiogenesis. |
S0014483520303675 | Although anti VEGF therapies have radically changed clinical practice there is still an urgent demand for novel integrative approaches for sight threatening retinal vascular diseases . As we hypothesize that protein tyrosine kinases are key signaling mediators in retinal vascular disease we performed a comprehensive activity based tyrosine kinome profiling on retinal tissue of 12 week old Akimba mice a translational model displaying hallmarks of early and advanced diabetic retinopathy . Western blotting was used to confirm retinal tyrosine kinase activity in Akimba mice . HUVEC tube formation and murine organotypic choroidal sprouting assays were applied to compare tyrosine kinase inhibitors with different specificity profiles . HUVEC toxicity and proliferation were evaluated using the CellTox Green Cytotoxicity and PrestoBlue Assays . Our results indicate a shift of the Akimba retinal tyrosine kinome towards a hyperactive state . Functional network analysis of significantly hyperphosphorylated peptides and upstream kinase prediction revealed a central role for Src FAK family kinases . Western blotting confirmed hyperactivity of this signaling node in the retina of Akimba mice . We demonstrated that not only Src but also FAK family kinase inhibitors with different selectivity profiles were able to suppress angiogenesis | Retinal tyrosine kinome profiling reveals hyperactivity in diabetic Akimba mice. Functional network analysis identifies Src FAK family kinases as central node. Specific Src family kinase inhibition potently suppresses. angiogenesis. |
S0014483520303687 | In this study we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction surgery . We investigated the biomechanical effect of ultraviolet A riboflavin cross linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy . Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery . Experimental models were established by superimposing the corneal lenticule strips until their thickness reached close to 500m . Corneal cross linking was performed subsequently using standard or accelerated protocol . Elasticity and viscosity were quantified using stress strain extensometer . TEM was used to visualize the collagen fiber diameter and interfibrillar spacing . The relative change in Young s modulus decreased nonlinearly with increasing stromal depth both in the standard and accelerated groups . Compared to the sham controls the rel . E in standard and accelerated CXL groups increased significantly in the anterior 400m and 275m depth respectively . Also the relative change in stress was significantly lower after standard and accelerated CXL compared to sham controls . Depth analysis showed similar results for the elastic effect . TEM images showed a small non significant increase in fibril diameter . The interfibrillar spacing decreased significantly after standard and accelerated CXL in the anterior mid stromal region . We noted that the increase of corneal stiffness correlated with decrease in interfibrillar spacing after CXL . The stiffening effect was depth dependent . The effect of accelerated CXL was less in the deep corneal stromal regions compared to standard CXL . | Biomechanical property changes are based on corresponding changes in morphology. The increase of corneal stiffness correlated with decrease in interfibrillar spacing. The stiffening effect was depth dependent after Collagen crosslinking. |
S0014483520303717 | The development of the eye requires the co ordinated integration of optical and neural elements to create a system with requisite optics for the given animal . The eye lens has a lamellar structure with gradually varying protein concentrations that increase towards the centre creating a gradient refractive index or GRIN . This provides enhanced image quality compared to a homogeneous refractive index lens . The development of the GRIN during ocular embryogenesis has not been investigated previously . This study presents measurements using synchrotron X ray Talbot interferometry and scanning electron microscopy of chick eyes from embryonic day 10 midway through embryonic development to E18 a few days before hatching . The lens GRIN profile is evident from the youngest age measured and increases in magnitude of refractive index at all points as the lens grows . The profile is parabolic along the optic axis and has two distinct regions in the equatorial plane . We postulate that these may be fundamental for the independent central and peripheral processes that contribute to the optimisation of image quality and the development of an eye that is emmetropic . The spatial distributions of the distinct GRIN profile regions match with previous measurements on different fibre cell groups in chick lenses of similar developmental stages . Results suggest that tissue compaction may not be necessary for development of the GRIN in the chick eye lens . | Refractive index gradient in chick lens is evident in the embryonic lens at day 10. The gradient is parabolic along the optic axis and biphasic in the equatorial plane. Tissue compaction does not appear to pay a role in formation of the gradient. |
S0014483520303729 | Hyperosmolarity is pro inflammatory stress to the ocular surface epithelium associated with dry eye disease . Astaxanthin is a kind of carotene which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis inflammatory bowel disease sepsis rheumatoid arthritis gastric inflammation brain inflammatory diseases . The aim of this study was to characterize the protective effect and potential mechanism of AST on DED | Hyperosmolarity induced the expression of HMGB1 and inflammatory cytokine in dry eye model. Astaxanthin decreased the expression of HMGB1 and inflammatory cytokines in dry eye model under hyperosmolarity. PI3K Akt signaling pathway may participate in the expression of HMGB1 and the protection of astaxanthin in dry eye. Astaxanthin might be a promising natural derivative for protecting ocular surfaces in dry eye. |
S0014483520303730 | The corneal endothelium is the inner cell monolayer involved in the maintenance of corneal transparence by the generation of homeostatic dehydration . The glycosaminoglycans of the corneal stroma develop a continuous swelling pressure that should be counteracted by the corneal endothelial cells through active transport mechanisms to move the water to the anterior chamber . Protein transporters for sodium Na | and. genes are expressed in human corneal endothelial cells at mRNA and protein levels. gene expression is upregulated in fetal samples. gene expression is upregulated in PPCD and FECD samples. gene expression is downregulated in fetal samples. gene expression is upregulated in FECD samples. |
S0014483520303742 | Tears have a vital function to protect and lubricate the ocular surface . Tear production distribution and clearance is tightly regulated by the lacrimal functional unit to meet ocular surface demands . The tear film consists of an aqueous mucin layer containing fluid and soluble factors produced by the lacrimal glands and mucin secreted by the goblet cells that is covered by a lipid layer . The array of proteins glycoproteins and lipids in tears function to maintain a stable well lubricated and smooth optical surface . Tear factors also promote wound healing suppress inflammation scavenge free radicals and defend against microbial infection . Disease and dysfunction of the LFU leads to tear instability increased evaporation inflammation and blurred and fluctuating vision . The function of tear components and the consequences of tear deficiency on the ocular surface are reviewed . | The complex structure and composition of the tear film protects the cornea promotes wound healing and maintains eye comfort and quality vision. The integrated lacrimal functional unit regulates tear production and maintains stability. Altered tear composition and stability in dry eye cause eye inflammation corneal disease and blurred vision. |
S0014483520303754 | Platelet derived growth factor is associated with clinical proliferative vitreoretinopathy which is characterized by formation of sub or epi retinal membranes that consist of cells including retinal pigment epithelial RPE cells and extracellular matrix . RPE cells play an important role in PVR pathogenesis . Previous findings indicated that PDGF receptor was essential in experimental PVR induced by fibroblasts . In RPE cells derived from epiretinal membranes from patients with PVR Akt was activated by PDGF B but not PDGF A which suggested that PDGFR was the predominant PDGFR isoform expressed in RPEMs . Indeed CRISPR Cas9 mediated depletion of PDGFR in RPEMs attenuated patient vitreous induced Akt activation and cellular responses intrinsic to PVR including cell proliferation migration and contraction . We conclude that PDGFR appears to be the PVR relevant PDGFR isoform in RPEMs . | The predominant PDGFR isoform in RPE cells isolated from PVR membranes is PDGFR. Depletion of PDGFR. in RPEMs suppresses vitreous stimulated Akt activation and cell contraction. PDGFR. is a potential target for PVR therapy. |
S0014483520303766 | Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects . However most current tests evaluating the integrity of retinal ganglion cells and optic nerve are based on rodent animal models . We aimed to evaluate and optimize the | We established a system to test optic nerve s integrity in Goats and rhesus macaques. Anesthesia with isoflurane resulted in more reproducible FVEP than xylazine in goats. Anesthesia with xylazine resulted in more reproducible PERG than xylazine in goats. Intra ocular crosstalk of PERG was undetectable in goats. Large Ganzfeld stimulator resulted in more reproducible FVEP than minimized one. |
S0014483520303778 | Primary angle closure glaucoma and retinitis pigmentosa can co occur but the mechanism of their association is not yet established . The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP and to determine the association between PACG and RP . Patients with early onset PACG with or without RP were selected from the glaucoma outpatient department after full ocular examinations by the same glaucoma specialist . Ocular biometry parameters were statistically analyzed . Blood samples were collected from the probands and genomic DNA was sent out for whole exome sequencing . Variants in 326 selected genes were extracted from the whole exome sequencing data and filtered using multiple bioinformatics analysis . The 326 genes included 10 PACG associated genes from two genome wide association studies 45 genes associated with anterior segment dysgenesis microcornea and microphthalmia and 271 RetNet genes . Potential pathogenic variants were obtained and underwent further genotypephenotype analysis . As a result a total of 32 probands with early onset PACG were collected nine had accompanying RP . No significant differences were noted for ocular biometry parameters between patients with PACG with RP and with PACG alone . Systematic analysis of the variants revealed that 16 of 32 probands carried PPV in 15 of 326 genes including 14 RetNet genes and one anterior segment dysgenesis associated gene . Of these 16 probands with PPV five were from the group of nine probands with both had PACG and RP and 11 were from the group of 23 probands with PACG alone . Of the 15 genes five genes | Ocular biometry parameters were similar between the patients with PACG alone and with PACG accompanied by RP. The c.1841G T in CRB1 was associated with the combination of RP and glaucoma. Variants in RetNet genes associated with patients with PACG with or without RP. |
S001448352030378X | Myofibroblast transformation of human Tenon s fibroblasts severely challenges the outcome of glaucoma filtration surgery . epigallocatechin 3 gallate is considered as a potential reagent to overcome this issue for its anti fibrosis effect on various human diseases but it is unclear on the fibrosis of Tenon s fibroblasts . This study was conducted to investigate the effect of EGCG on TGF 1 induced myofibroblast transformation of human Tenon s fibroblasts . The human Tenon s fibroblasts were incubated in the medium containing 10ng mL TGF 1 and subsequently treated with EGCG or mitomycin C . The cell proliferation and migration were analyzed . The expression of alpha smooth muscle actin type I collagen and p Smad2 3 were also evaluated . It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF 1 alone . Scratch Wound assay showed that 48h after TGF 1 induction only 10 of the wound width remained . But cells treated with EGCG still showed over 93 wound width . Further EGCG effectively inhibited TGF 1 induced expression of SMA and Col I as well as phosphorylation of Smad2 3 in Tenon s fibroblasts . Altogether we concluded that EGCG suppressed the myofibroblast transformation in Tenon s fibroblasts through inactivating TGF 1 Smad signaling . These findings demonstrate that EGCG can be considered as one of the possible antifibrotic reagents for preventing postoperative scarring in glaucoma filtration surgery . | EGCG markedly attenuates the proliferation and migration of Tenon s fibroblasts. EGCG inhibits TGF 1 induced myofibroblast transition in Tenon s fibroblasts. EGCG is a potential reagent against postoperative scarring in glaucoma surgery. |
S001448352030381X | Optical coherence tomography angiography is a rapidly developing technique which generates angiographic images non invasively . This study proposes a method to determine the vessel density in OCTA scans in general and especially the local peripapillary vessel density . The method produces vessel density heatmaps that contain information about the local vessel density . We apply the method in a small study to demonstrate its applicability and its potential to investigate the influence of local conditions on the vessel density . In the study we combine information from enhanced depth imaging optical coherence tomography about the location of optic disc drusen with information from OCTA about the vessel density . We see a reduction in local peripapillary vessel density in peripapillary sections with a large volume of ODD . | The developed vessel density heatmaps enables investigation of local vessel density. Large optic disc drusen volume results in low local peripapillary vessel density. Investigation of the impact on vessel density from local anatomic conditions. Multiplexed optical coherence tomography imaging. |
S0014483520303821 | Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation . To reduce the recurrence rate surgery is the main strategy in combination with adjacent procedures or adjunctive therapy . One of the most common adjunctive agents mitomycin C is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications . A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low density lipoprotein receptors . In this study we designed and synthesized MMC loaded mesoporous silica nanoparticles conjugated with LDL | LDL is conjugated with mitomycin C loaded nanoparticles for targeted delivery. Activated pterygium fibroblasts uptake more targeted nanoparticles. LDL targeted MMC shows a good antiproliferative effect on pterygium fibroblasts. LDL targeted MMC shows a lower toxicity to normal fibroblasts. |
S0014483520303833 | To identify the feasibility of reconstructing corneal endothelial sheets by seeding non infected monoclonal human corneal endothelial cells onto porcine Descemet s membrane and verifying the function in vitro and in vivo . Denuded porcine DM was decellularized for haematoxylin and eosin staining and DNA was removed via incubation with ethylene glycol diglycidyl ether . The physical properties of the incubated DMs were evaluated and compared to those of unincubated DMs . The non infected monoclonal HCECs were examined by chromosome analysis and the cell proliferation was evaluated by BrdU labelling . Then HCECs at passage 30 were then seeded on the DM and cultured for approximately 5 days . The cell growth density and expression of the sodium potassium adenosine triphosphatase . Results of chromosome analysis shown the number of the HCEC cell line was still 46 and no abnormal chromosome structure was found . BrdU labelling shown the HCECs stopped proliferating after 5 days and the cells formed a single layer . The cells transferred to porcine DM formed tight connections with the substrate and generated layers of hexagonal cells on day 5 . Adjacent cells cultivated on DM were closely attached to each other tightly adhered to the porcine DM and expressed the Na Seeding non infected monoclonal HCECs on porcine DM could reconstruct functional corneal endothelial sheets . These results may help uncover new applications for tissue engineered endothelium in endothelial keratoplasty . | Human corneal endothelial cells HCECs cultured on porcine Descemets membrane DM expressed functional proteins. Corneas received the reconstructed HCEC sheets became transparency after Descemets membrane endothelial keratoplasty DMEK . The corneal thickness and the density of corneal endothelial cells were similar to normal corneas after DMEK. 98 days after surgery cells on the transplanted sheets were dense and tightly adhered to the porcine DM. |
S0014483520303857 | The cornea is an avascular transparent ocular tissue that serves as a refractive and protective structure for the eye . Over 90 of the cornea is composed of a collagenous rich extracellular matrix within the stroma with the other 10 composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers at the anterior and posterior cornea respectively . Due to its prominent role in corneal structure tissue engineering approaches to model the human cornea | 3 dimensional corneal tissue models more closely re capitulate the human cornea. Co culture approaches can be applied to develop a full thickness cornea. Advances in bioprinting have allowed the development of a printed human cornea. Vitamin C promotes significant collagen deposition by corneal fibroblasts. Self assembled stromal models generate a 65m thick matrix over 11 weeks. |
S0014483520303869 | Circular RNA Homeodomain Interacting Protein Kinase 3 was found to involve in the pathogenesis of age related cataract . Here we further disclosed the related target genes and molecular mechanism of circHIPK3 in the ARC progression . The expression of circHIPK3 microRNA 2213p was detected using the quantitative real time polymerase chain reaction . Human lens epithelial cell proliferation and apoptosis were measured by 3 dimethylthiahiazo 3 5 di phenytetrazoliumromide assay and flow cytometry respectively . Western blot was used to detect the levels of apoptosis related proteins and phosphoinositide 3 kinase p protein kinase B pathway related proteins . Levels of malondialdehyde and glutathione peroxidase were measured by kits . The interaction between miR 2213p and circHIPK3 was confirmed by dual luciferase reporter assay and RNA immunoprecipitation assay . CircHIPK3 was down regulated while miR 2213p was up regulated in human lens epithelium samples of ARC patients . CircHIPK3 up regulation or miR 2213p down regulation mediated the promotion of proliferation inhibition of apoptosis decrease of MDA level as well as increase of GSH PX level in HLECs . MiR 2213p was a target of circHIPK3 and miR 2213p overexpression reversed the protective action of circHIPK in HLEC functions . In addition circHIPK3 activated PI3K AKT pathway via regulating miR 2213p and silencing miR 2213p protected HLECs from dysfunction by activating PI3K AKT pathway . We demonstrated that circHIPK3 protected HLECs from dysfunction by regulating miR 2213p PI3K AKT pathway indicating a new insight into the pathogenesis of ARC and providing a potential therapeutic target for ARC . | CircHIPK3 is down regulated while miR 2213p is up regulated in human lens epithelium samples of ARC patients. CircHIPK3 protects HLECs from dysfunction. MiR 2213p aggravates the damage of HLECs. MiR 2213p is a target of circHIPK3 and regulates the activation of PI3K AKT pathway. CircHIPK3 miR 2213p PI3K AKT pathway involves in the modulation of HLEC dysfunction. |
S0014483520303870 | Formation of the eye lens depends on the continuous differentiation of lens epithelial cells into lens fiber cells . To attain their mature structure and transparent function nascent lens fiber cells must complete a precise cellular remodeling program hallmarked by the complete elimination of organelles to form the core lens organelle free zone . Lacking a blood supply the lens resides in a hypoxic environment that results in a decreasing oxygen concentration from the lens surface to the lens core . This oxygen gradient results in a hypoxic microenvironment in the region of the lens where immature lens fiber cells initiate loss of organelles to form the core OFZ . These features of the lens suggest a potential role for low lens oxygen levels in the regulation of organelle degradation and other events critical for mature lens fiber cell formation . Hypoxia activates the master regulator of the hypoxic response hypoxia inducible factor 1a that regulates hypoxia responsive genes . To identify a potential role for hypoxia and HIF1a in the elimination of organelles during lens fiber cell maturation we tested the requirement for hypoxia in the degradation of non nuclear organelles in | Hypoxia activates HIF1a in the eye lens. HIF1a regulates lens BNIP3L expression. Hypoxia and HIF1a regulate degradation of lens non nuclear organelles. |
S0014483520303882 | CLN2 neuronal ceroid lipofuscinosis is a hereditary neurodegenerative disorder characterized by progressive vision loss neurological decline and seizures . CLN2 disease results from mutations in | Progressive retinal degeneration occurs in CLN2 neuronal ceroid lipofuscinosis. Retinal degeneration results from deficiency in lysosomal enzyme TPP1. Periodic intravitreal injection of recombinant TPP1 preserves retinal structure and function. |
S0014483520303894 | The retina is one of the most metabolically active tissues yet the processes that control retinal metabolism remains poorly understood . The mTOR complex that drives protein and lipid biogenesis and autophagy has been studied extensively in regards to retinal development and responses to optic nerve injury but the processes that regulate homeostasis in the adult retina have not been determined . We previously demonstrated that normal adult retina has high rates of protein synthesis compared to skeletal muscle associated with high levels of mechanistic target of rapamycin a kinase that forms multi subunit complexes that sense and integrate diverse environmental cues to control cell and tissue physiology . This study was undertaken to 1 quantify expression of mTOR complex 1 and mTORC2 specific partner proteins in normal adult rat retina brain and liver and 2 to localize these components in normal human rat and mouse retinas . Immunoblotting and immunoprecipitation studies revealed greater expression of raptor and rictor in normal rat retina relative to liver or brain as well as the activating mTORC components pSIN1 and pPRAS40 . By contrast liver exhibits greater amounts of the mTORC inhibitor DEPTOR . Immunolocalization studies for all three species showed that mTOR raptor and rictor as well as most other known components of mTORC1 and mTORC2 were primarily localized in the inner retina with mTORC1 primarily in retinal ganglion cells and mTORC2 primarily in glial cells . In addition phosphorylated ribosomal protein S6 a direct target of the mTORC1 substrate ribosomal protein S6 kinase beta 1 was readily detectable in RGCs indicating active mTORC1 signaling and was preserved in human donor eyes . Collectively this study demonstrates that the inner retina expresses high levels of mTORC1 and mTORC2 and possesses active mTORC1 signaling that may provide cell and tissue specific regulation of homeostatic activity . These findings help to define the physiology of the inner retina which is key for understanding the pathophysiology of optic neuropathies glaucoma and diabetic retinopathy . | mTORC1 and mTORC2 and component proteins are highly expressed in normal adult rat retina compared to brain and liver. mTORC1 and ribosomal protein S6 are localized primarily to retinal ganglion cells of human rat and mouse retinas. mTORC2 localizes primarily in retinal glial cells of post mortem human eyes and adult rat and mouse retinas. TSC1 and TSC2 are found in both mTORC1 and mTORC2 from rat retina. |
S0014483520303900 | To quantify short term microvascular changes after pars plana vitrectomy with internal limiting membrane peeling in patients with idiopathic macular hole using optical coherence tomography angiography . Cohort Study . This study included patients with IMH . Affected eyes were compared with fellow eyes . 66mm OCTA images of the study eye and fellow eye were acquired one day before surgery 4 weeks and 12 weeks after surgery . Microvascular alterations in the superficial and deep capillary plexus were assessed by measuring vessel density and the shortest distance to the surrounding vessels of all intercapillary pixels . Only vessels enclosed by an ETDRS Grid centered on the fovea were analyzed . Change of vessel density and vessel distance to baseline . OCTA images of the 15 study and 15 fellow eyes of 15 included patients were analyzed and revealed a significant increase in vessel density and decrease in vessel distance of the deep capillary plexus in study eyes 4 weeks after surgery compared to baseline . Our superficial capillary plexus findings were the inverse namely a significant decrease in vessel density and increase in vessel distance . Postoperative microvascular changes proved to be closely associated with the extent of retinal thickness reduction in the perifoveal deep capillary plexus . IMH closure after PPV and ILM peeling caused a significantly improved microvasculature in the deep capillary plexus which may represent reorganized perifoveal microvasculature due to the regression of cystoid spaces . | Microvascular changes do appear after macular hole closure. The deep vascular plexus showed improved microvasculature after surgery. Regression of intraretinal cystoid spaces could explain those changes. |
S0014483520303912 | Retinal ischemia leads to an early severe damage of the retina and thus plays an important role in eye diseases such as angle closure glaucoma or retinal vascular occlusion . In retinal diseases there is common sense about the affection of the optic nerve by ischemic injury . However the exact dynamic processes of this optic nerve degeneration are mainly unclear . In this study retinal ischemia was induced in one eye of Brown Norway rats by raising the intraocular pressure 60min to 140mmHg followed by natural reperfusion . Optic nerves were analyzed at six different points in time 2 6 12 and 24h as well as 3 and 7 days after ischemic injury . Cell infiltration and moreover signs of tissue demyelination and dissolution were noticed in optic nerves 7 days after ischemia . Although microglial activation was verified already from 12h on after ischemia the beginning of a structural degeneration of the neurofilament was seen at 3 days . Interestingly proliferative microglia were present later on . At this point the number of total microglia was also increased in ischemic nerves . Concluding our data indicate that not only retinal tissue is affected by an ischemia the optic nerve also demonstrates progressive damage . Interestingly a microglia activation was noted days before structural damage became visible . | Structural alterations and demyelination are detectable in the optic nerve at the earliest 3 days after ischemic injury. The microglia activation in the optic nerve starts already days before the later onset of the structural damage. Results indicate that the optic nerve degenerates subsequently after retinal damage induced by ischemia. |
S0014483520303924 | Imaging mass spectrometry enables targeted and untargeted visualization of the spatial localization of molecules in tissues with great specificity . The lens is a unique tissue that contains fiber cells corresponding to various stages of differentiation that are packed in a highly spatial order . The application of IMS to lens tissue localizes molecular features that are spatially related to the fiber cell organization . Such spatially resolved molecular information assists our understanding of lens structure and physiology however protein IMS studies are typically limited to abundant soluble low molecular weight proteins . In this study a method was developed for imaging low solubility cytoskeletal proteins in the lens a tissue that is filled with high concentrations of soluble crystallins . Optimized tissue washes combined with on tissue enzymatic digestion allowed successful imaging of peptides corresponding to known lens cytoskeletal proteins . The resulting peptide signals facilitated segmentation of the bovine lens into molecularly distinct regions . A sharp intermediate filament transition from vimentin to lens specific beaded filament proteins was detected in the lens cortex . MALDI IMS also revealed the region where posttranslational myristoylation of filensin occurs and the results indicate that truncation and myristoylation of filensin starts soon after filensin expression increased in the inner cortex . From intermediate filament switch to filensin truncation and myristoylation multiple remarkable changes occur in the narrow region of lens cortex . MALDI images delineated the boundaries of distinct lens regions that will guide further proteomic and interactomic studies . | New tissue preparation allows imaging mass spectrometry of lens cytoskeletal proteins. Imaging mass spectrometry shows distinct molecular zones across lens. Location of intermediate filament switch in lens cortex revealed in images. |
S0014483520303948 | The outcomes of refractive surgical procedures to improve uncorrected vision in patientsincluding photorefractive keratectomy laser in situ keratomileusis Small Incision Lenticule Extraction and corneal inlay proceduresis in large part determined by the corneal wound healing response after surgery . The wound healing response varies depending on the type of surgery the level of intended correction of refractive error the post operative inflammatory response generation of opacity producing myofibroblasts and likely poorly understood genetic factors . This article details what is known about these specific wound healing responses that include apoptosis of keratocytes and myofibroblasts mitosis of corneal fibroblasts and myofibroblast precursors the development of myofibroblasts from keratocyte derived corneal fibroblasts and bone marrow derived fibrocytes deposition of disordered extracellular matrix by corneal fibroblasts and myofibroblasts healing of the epithelial injury and regeneration of the epithelial basement membrane . Problems with epithelial and stromal cellular viability and function that are altered by corneal inlays are also discussed . A better understanding of the wound healing response in refractive surgical procedures is likely to lead to better treatments to improve outcomes limit complications of keratorefractive surgical procedures and improve the safety and efficiency of refractive surgical procedures . | Wound healing is a major determinate of outcomes for corneal refractive surgery. The corneal wound healing response varies with the type of corneal refractive surgery. The risk of scarring fibrosis haze increases with higher levels of correction after PRK. LASIK is rarely associated with haze because the central epithelial basement membrane is preserved. |
S001448352030395X | No other tissue in the body depends more on the composition and organization of the extracellular matrix for normal structure and function than the corneal stroma . The precise arrangement and orientation of collagen fibrils lamellae and keratocytes that occurs during development and is needed in adults to maintain stromal function is dependent on the regulated interaction of multiple ECM components that contribute to attain the unique properties of the cornea transparency shape mechanical strength and avascularity . This review summarizes the contribution of different ECM components their structure regulation and function in modulating the properties of the corneal stroma . Fibril forming collagens fibril associated collagens with interrupted triple helices network forming collagens as well as small leucine rich proteoglycans expressed in the stroma decorin biglycan lumican keratocan and fibromodulin are some of the ECM components reviewed in this manuscript . There are spatial and temporal differences in the expression of these ECM components as well as interactions among them that contribute to stromal function . Unique regions within the stroma like Bowman s layer and Descemet s layer are discussed . To define the complexity of corneal stroma composition and structure as well as the relationship to function is a daunting task . Our knowledge is expanding and we expect that this review provides a comprehensive overview of current knowledge definition of gaps and suggests future research directions . | The unique corneal stromal structure and function is regulated by different extracellular matrix components. The stroma proper as well as Bowman and Descemetslayers have unique ECM compositions and functions. Regulated collagen fibril formation is critical for stromal structure and function. ECM molecules including SLRPs regulate stromal fibrillogenesis hydration and the availability of growth factors. Regulation of ECM components play a major role in wound healing. |
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