Filename
stringlengths 17
17
| Abstract
stringlengths 76
3.38k
| Highlights
stringlengths 80
1.73k
|
|---|---|---|
S0014483520303961 | Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells the extracellular matrix and gene expression in the nucleus . Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their | Current knowledge on the expression and function of integrins in corneal health and disease is summarized. Integrins mediate adhesion of corneal epithelial and endothelial cells to their respective basement membranes. This is the first review to discuss similarities and differences in the integrins expressed by both cell types. |
S0014483520303973 | Corneal dystrophies represent a heterogenous group of genetic diseases . The International Committee of Classification of Corneal Dystrophies distinguishes between 22 distinct forms of corneal dystrophy which are predominantly autosomal dominant although autosomal recessive and X chromosomal dominant and recessive patterns do exist . A detailed corneal examination of as many affected family members as possible can show the phenotypic differences of the various generations . There are few publications which describe the different CDs with regard to the early and late phenotypes . According to early and late phenotype three types of CD are generally classified Thirteen CDs with early and late clinical landmarks . However it must be pointed out that the different penetrances of the gene often leads to quantitative differences in the corneal phenotype in peers in distinct generations of the same family . Seven CDs with late onset and very little progression of the corneal changes . Two CDs with congenital haze which can be interpreted as the final phenotype of this dystrophy . This applies to autosomal dominant and recessive inheritance . | Early and late clinical landmarks of corneal dystrophies. Classification of corneal dystrophies with regard to their clinical landmarks. Influence of the different penetrances of the gene on the clinical landmarks of corneal dystrophy. Corneal dystrophies with very low clinical progression. Corneal dystrophies with congenital haze. |
S0014483520303985 | Eyelid basal cell carcinoma is the most common eyelid malignancy . Metabolic reprogramming is critical in tumorigenesis but the metabolic feature of eyelid BCC remains elusive . In this study we aim to reveal the metabolic profile in eyelid BCC using targeted metabolomics . Eyelid samples were collected from patients who had removal of BCC and from control patients who underwent blepharoplasty . Multivariate analysis of metabolomics data distinguished the two groups indicating that eyelid BCC has significantly different metabolome than the healthy tissue . We found 16 increased and 11 decreased metabolites in the BCC tissues . These metabolites were highly enriched in the metabolism of nicotinamide adenine dinucleotide glutathione metabolism polyamine metabolism and the metabolism of glycine serine threonine arginine and proline . amino acid metabolism . Metabolites from NAD metabolism had the highest sensitivity specificity and prediction accuracy in a prediction model for eyelid BCC . In conclusion eyelid BCC has a signature change of cell metabolome . Metabolites in NAD metabolic pathways could potentially be biomarkers or therapeutic targets for eyelid BCC . | Using targeted metabolomics we reveal metabolic features in the most common eyelid malignancy basal cell carcinoma BCC . Eyelid BCC alters NAD metabolism glutathione metabolism polyamine metabolism and amino acid metabolism. Metabolites in NAD pathways are potential biomarkers and therapeutic targets for eyelid BCC. |
S0014483520303997 | Diabetic retinopathy is the most common complication of diabetes . Proliferative DR is a more advanced stage of DR which can cause severe impaired vision and even blindness . However the precise pathological mechanisms of PDR remain unknown . DNA methylation serves an important role in the initiation and progression of numerous types of disease including PDR . The purpose of this study was to identify the aberrantly methylated differentially expressed genes as potential therapeutic targets of PDR . The gene expression microarray dataset GSE60436 and the methylation profiling microarray dataset GSE57362 were used to determine the aberrantly methylated DEGs in PDR utilizing normal retinas as controls and fibrovascular membranes in patients with PDR as PDR samples . The functional term and signaling pathway enrichment analysis of the selected genes were subsequently performed . In addition protein protein interaction networks were constructed to determine the hub genes and the network of transcriptional factor and target hub genes was also analyzed . In total 132 hypomethylated genes were found to be upregulated whereas 172 hypermethylated genes were discovered to be downregulated in PDR . The hypomethylated upregulated genes were found to be enriched in the pathways such as cell substrate adhesion adherens junction cell adhesion molecule binding and extracellular matrix receptor interactions . Meanwhile the hypermethylated downregulated genes were enriched in the pathways such as visual perception presynapse and the synaptic vesicle cycle . Based on the PPI analysis a total of eight hub genes were identified | The present study was the first integrative analysis of DNA methylation alterations and gene expression differences in PDR. Numerous aberrantly methylated differentially expressed genes were screened between PDR patients and healthy participants. 8 hub genes. were identified as potential diagnosis targets. |
S0014483520304048 | To examine the protective effects of Isoliquiritigenin in angiotensin II induced inflammation and fibrosis on Human Tenon s capsule Fibroblasts and Mouse Peritoneal Macrophages . This study also investigated the potential mechanism of action of ISL . Methyl thiazolyl tetrazolium assay was used to test ISL toxicity . An ELISA and an RT qPCR assay detected the inflammatory cytokines . A Western blot investigated the expression levels of inflammation related signals Pre treatment with ISL dose dependently decreased the mRNA levels of TNF IL 6 ICAM 1 and COX 2 induced by ANG II in both MPMs and HTFs . ANG II remarkably increased the amount of P65 in the nuclei and decreased the amount of P65 in the cytoplasm . Additionally ANG II reduced PPAR expression levels in a time dependent manner . Furthermore these effects which were induced by ISL were remarkably neutralized by ISL pre treatment . Finally ANG II markedly elevated the expression of fibronectin and SMA . ISL could alleviate ANG II induced fibrogenesis by inhibiting the NF B PPAR inflammatory pathway . In addition ISL may be a potential agent for the treatment of conjunctival fibrosis . Most importantly the NF B PPAR signaling pathway could be an effective therapeutic target for the prevention and treatment of conjunctival fibrosis after glaucoma surgery . | ISL reduced Angiotensin II mediated inflammation in MPMs and HTFs. ISL prevented inflammation by inhibiting NF B PPAR inflammatory pathway. ISL attenuated Angiotensin II induced fibrogenesis in HTFs. NF B PPAR may be a key target in conjunctival fibrosis after trabeculectomy. ISL may be the potential agent to cure conjunctival fibrosis after trabeculectomy. |
S001448352030405X | To compare disease severity in detail between patients carrying variants in exons 114 and ORF15 of retinitis pigmentosa GTPase regulator Systematic next generation sequencing data analysis Sanger sequencing validation and segregation analysis were utilised to identify the pathogenic variants . Detailed ophthalmic examinations including electroretinograms fundus photography fundus autofluorescence and optical coherence tomography were performed . Statistical analysis including age adjustment and comparison were performed based on cross sectional level to compare disease severity between variants in the two Sixty two variants were identified in Patients with variants in exons 114 retained less visual acuity than patients with ORF15 variants and deteriorated faster . However the ellipsoid zone widths central retinal thickness and refractions were comparable between the two groups . Autofluorescence pattern relates to the age and the variant grouping . | The paper described phenotypic variability in a large cohort of 86 Chinese patients from 77 unrelated families with mutations in. gene. We focused on comparing disease severity between variants in two predominant retinal. isoforms by assessing different retina function parameters in detail. At a given age patients with variants in exons 114 retained less visual acuity than patients with ORF15 variants and progressed at a faster rate. The visual fields EZWs and refractions are comparable between the two variant groups. |
S0014483520304061 | The central nervous system and the eye are involved in Human immunodeficiency virus related disease . Although optic nerve is considered an extension of the CNS it has not been systematically evaluated to determine if infections of brain can extend into the eye or vice versa . The brain and posterior compartment of eyeball retrieved at autopsy of patients succumbing to NeuroAIDS were evaluated with Hematoxylin Eosin special stains and immunohistochemistry for infective pathogens . Multiplex PCR was performed in vitreous CSF and serum for simultaneous detection of bacterial viral and protozoal opportunistic infections . Ocular involvement in NeuroAIDS was seen in 93.7 with opportunistic infection being the most common 62.5 with toxoplasma optic neuropathy in 5 Cryptococcal optic neuritis in 3 and Cytomegalovirus chorioretinitis in 2 . Concordance between ocular and CNS pathology was seen in 50 of cases . CSF PCR was more sensitive than PCR in vitreous for detecting ocular infections in posterior compartment of eye . | First study to evaluate both ocular and CNS pathology in HIV AIDS for detecting opportunistic infections by multiplex PCR. Ocular manifestations were common in cases of NeuroAIDS even in the absence of clinical symptoms of ocular involvement. CSF PCR was more sensitive than vitreous PCR in detecting posterior chamber pathology. |
S0014483520304073 | The retina acts as an independent clock informing the central pacemaker the suprachiasmatic nucleus under environmental light conditions with consequences of such inputs for the central and peripheral nervous system . Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres . The retina possesses neuropeptides that act as neurotransmitters or neuromodulators . Alanyl aminopeptidase activity regulates some of these neuropeptides and therefore reflects their function . We analyzed AlaAP activity in the left and right retinas of adult male rats at successive time points under standard and nonstandard conditions . AlaAP activity was measured fluorometrically using alanyl beta naphthylamide as the substrate . Under standard conditions there were no differences in the left or right retina between time points with the left retina predominating particularly in the light period . In contrast under constant light no left versus right differences were observed but significant differences between time points appeared . In comparison with standard conditions constant conditions led to significantly higher AlaAP activity . Considering all the left retina data in comparison with all the right retina data no correlation was found between the left and right retinas under standard conditions but a significant positive correlation was observed under constant light . These results demonstrate an asymmetrical response of retinal AlaAP activity to changes in environmental light conditions which may affect the functions in which the substrates of AlaAP are involved and the information projected to the brain hemispheres . | The eyes are the only way of entering light information in mammals. Retinal neuropeptidergic function may modulate the information sent to brain hemispheres. Some retinal neuropeptides are regulated by AlaAP activity. Retinal AlaAP activity responds asymmetrically to changes in environmental light. Asymmetry in retinal AlaAP activity may influence the information sent to the brain. |
S0014483520304085 | To avoid negative environmental impacts of escapees and potential inter breeding with wild populations the Atlantic salmon farming industry has and continues to extensively test triploid fish that are sterile . However they often show differences in performance physiology behavior and morphology compared to diploid fish with increased prevalence of vertebral deformities and ocular cataracts as two of the most severe disorders . Here we investigated the mechanisms behind the higher prevalence of cataracts in triploid salmon by comparing the transcriptional patterns in lenses of diploid and triploid Atlantic salmon with and without cataracts . We assembled and characterized the Atlantic salmon lens transcriptome and used RNA seq to search for the molecular basis for cataract development in triploid fish . Transcriptional screening showed only modest differences in lens mRNA levels in diploid and triploid fish with few uniquely expressed genes . In total there were 165 differentially expressed genes between the cataractous diploid and triploid lens . Of these most were expressed at lower levels in triploid fish . Differential expression was observed for genes encoding proteins with known function in the retina and proteins associated with repair and compensation mechanisms . The results suggest a higher susceptibility to oxidative stress in triploid lenses and that mechanisms connected to the ability to handle damaged proteins are differentially affected in cataractous lenses from diploid and triploid salmon . | Increased prevalence of ocular cataracts in triploid Atlantic salmon. Modest transcriptional differences between diploid and triploid cataractous lenses. Retina associated genes were differentially affected. Ploidy influence ability to handle damaged proteins and protein turnover. Triploid lens may be more prone to oxidative damage and chemotactic cell movement. |
S0014483520304097 | Due to the unique anatomical structure of the eye ocular drug delivery is a promising delivery route for the treatment of several ocular diseases such as the ocular neovascularization that contributes to diabetic retinopathy . This disease is triggered by inflammation retinal ischemia and or deposits of advanced glycation end products as well as increased levels of vascular endothelial growth factor interleukins or reactive oxygen species . Gold has unique antioxidant and antiangiogenic properties and can inhibit angiogenic molecules . Furthermore gold nanoparticles are not only biocompatible they are easy to synthesize they absorb and scatter visible light and they can be made with precise control over size and shape . GNPs are an excellent candidate for ocular drug delivery because they can be conjugated to an extraordinarily diverse array of different biomolecules and surface functionalization can improve the mobility of GNPs across the physiological barriers of the eye such as the vitreous humour or the inner limiting membrane . For this purpose we employed low molecular weight hyaluronan to increase the mobility of the nanoparticles as well as target them to HA receptors that are expressed in different cells of the eye . In this study the combination of gold and HA enhanced the stability of the whole carrier and promoted their distribution across ocular tissues and barriers to reach the retina . Moreover analysis | Surface functionalization improves the pass of gold nanoparticles across eye barriers. Hyaluronan enhances the biodistribution of gold nanoparticles through the retina. Gold nanoparticles show protective and antiangiogenic effects in retinal models. Hyaluronan enhances stability of gold nanoparticles in different media and pHs. GNPs inhibit advanced glycated end products cell death and neovascularization. |
S0014483520304103 | Over the past century corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation . Although more than 80 of the corneal transplantations have favorable outcomes immune mediated rejection continues to be the major cause of failure in well over 50 of graft recipients that have inflamed and vascularized host beds . Over the past two decades the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies . In order to successfully test the efficacy of these interventions it is essential to model the immunological processes occurring as a consequence of corneal transplantation . Herein we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high risk corneal transplantation settings . We have also discussed the practical and technical differences as well as biological and immunological variations in different animal models . | These animal models are essential tools to elucidate the fundamental immunological mechanisms that govern corneal allograft rejection. These animal models are critical for the development of efficacious therapeutic modalities to improve long term graft survival. These models also deeply increase our understanding of the basis of ocular immunity with myriad applications beyond corneal transplantation. |
S0014483520304115 | Photoreceptor cells undergo changes with aging . It is unknown if their microtubules are stable or not with aging . This study examined photoreceptor cell ultrastructure from 18 human donor retinas and quantified the photoreceptors with altered microtubules over six to ninth decades in four defined retinal regions . In addition immunoreactivity to microtubule associated protein 2 tau and hyperphophorylated tau was performed in retinal sections from companion eyes . In young donor retinas below 75 years of age microtubules appeared straight in photoreceptor inner segments and axons . With age they appeared bent or misaligned in macular and mid peripheral photoreceptors . In addition dense granular materials were present in photoreceptor axons and synaptic terminals in advanced ages . In all decades rod microtubules were affected more than their cone counterparts . Both rods and cones were significantly affected in mid peripheral retina in eighth decade compared to other decades or retinal regions examined . IR showed a steady expression of MAP 2 in inner segments and tau in inner segments to axons below 75 years of age but was absent for both markers in scattered macular and mid peripheral photoreceptors in advanced ages . IR to hyperphosphorylated tau was present mainly in inner retina and increased with aging . Markers of oxidative stress e.g . lipid peroxidation and nitrosative stress were immunopositive in aged photoreceptors . The sporadic loss of MAP 2 and tau IR in photoreceptors may be due to microtubule changes all these changes may affect intracellular transport and be partly responsible for photoreceptor death in aged human retina . | Human photoreceptor microtubules alter with aging. Rod microtubules alter significantly more than cone counterparts. There is sporadic loss of MAP 2 and tau from macular photoreceptors. Hyperphosphorylated tau is expressed widely in aged human retina. |
S0014483520304127 | Astrocytes are critical for the maintenance of retinal ganglion cell axonal function and viability and form a key component of the functional neurovascular unit . Recently we described the quantitative properties of astrocytes in relation to the capillary distributions in optic nerve laminar regions . Here we provide a quantitative analysis of astrocytes and RGC axons in longitudinal sections of optic nerve tissue . Histological and immunocytochemical techniques are used to demonstrate the density of astrocytes RGC axons and glia neuron ratios across the pre laminar lamina cribrosa and post laminar compartments of the optic nerve head . A study of human pig horse and rat optic nerves was performed and comparisons are made between species . This study demonstrates that the distribution of astrocytes correlates closely with the density of axonal processes in accordance with the functional requirement of different regions of the ganglion cell axon . There was a consistency of glia neuron ratios in the majority of laminar compartments except for the human and rat prelaminar regions which demonstrated lower ratios of astrocyte to axonal processes . The distribution of astrocytes may reflect a functional susceptibility to development of disease in the prelaminar region of the optic nerve . Interspecies comparison at the lamina cribrosa showed strikingly consistent glia neuron ratios . Collectively our findings suggest there may be a critical ratio of glia to neuron needed to maintain healthy cellular physiology across different laminar compartments of the optic nerve with particular importance for the health of the lamina cribrosa region . It is possible that in disease processes the glia neuron relationships across the different laminar compartments may be perturbed and this may be relevant for the development of glaucoma . Emerging technologies may further aid our understanding in how the physiology of optic nerve tissue cellular structure may be affected by changes to ONH characteristics and elevated intraocular pressure induced damage . Such findings may also permit the early identification of RGC axonal injury by identifying quantifiable changes in structural tissue architecture when pathophysiological pathways predominate . | Glia neuron ratios were uniform across the majority of laminar compartments for all animal species studied. Interspecies comparison at the lamina cribrosa yielded strikingly consistent glia neuron ratios. The density of astrocytes correlate with the density of axonal processes in accordance with functional requirements. |
S0014483520304139 | Elevated level of interleukin 17 predominantly produced by T helper 17cells has been implicated in diabetic retinopathy but it remains unclear whether IL 17 is involved in the pathogenesis of DR. Ins2 | Akita GKO mice were established by crossbreeding Ins2. mice with IFN deficient mice. Th17 cell differentiation is promoted in Akita GKO mice more than GKO mice. VEGF production and leukostasis to the retinal vessels are increased in Akita GKO mice compared with Akita mice. Retinal morphological and functional changes are observed in Akita GKO mice at 9 week old. |
S0014483520304140 | Retinal vessels are at least in part involved in clearing of Fc terminus containing proteins from the vitreous . In vitro the Fc fusion protein aflibercept is transported through a monolayer of unchallenged immortalized bovine retinal endothelial cells mediated by the neonatal Fc receptor but part of the Fc fusion protein is also degraded . Aflibercept s target VEGF A not only enhances the permeability of REC by destabilization of tight junctions thereby allowing for paracellular flow it may also lower the intracellular stability of the Fc fusion protein by changing its binding properties to the FcRn . Therefore we investigated the transport and fate of aflibercept in VEGF A | VEGF A enhances aflibercept s passage through a monolayer of retinal endothelial cells. Passage of aflibercept is not dependent on the FcRn under these conditions. Exogenously added VEGF A is internalized and degraded by retinal endothelial cells. Aflibercept prevents uptake of VEGF A by retinal endothelial cells early after addition. VEGF A induced disturbances persist for nearly one day after addition of aflibercept. |
S0014483520304152 | Claudin 19 is the major claudin in the tight junctions of the retinal pigment epithelium . Claudin 3 is also uniformly expressed albeit in lesser amounts . Besides modulating transepithelial diffusion claudins modulate gene expression . The absence of claudin 19 and claudin 3 in the RPE cell lines ARPE 19 and hTERT RPE 1 provide an opportunity to examine whether exogenous claudins regulate gene expression in the absence of tight junctions . Quantitative RT PCR was used to compare gene expression in ARPE 19 and hTERT RPE 1 with that of highly differentiated human fetal RPE . Claudin 19 and claudin 3 were exogenously expressed using an adenoviral vector . The transepithelial electrical resistance was measured using Endohm electrodes and the effects of claudin on the actin cytoskeleton were determined by immunocytochemistry . The effect of claudin on gene expression was examined by quantitative RT PCR and western blotting . Aside from claudin 19 and claudin 3 ARPE 19 and hTERT RPE 1 expressed most junction associated mRNAs in amounts comparable to human fetal RPE but some RPE signature and maturation genes were under expressed . Unlike ARPE 19 hTERT RPE 1 failed to form tight junctions or develop a TER . Claudins exogenously expressed in hTERT RPE 1 failed to crystalize an apical junctional complex . Actin filaments were not redistributed from stress fibers to cortical bands and a TER was not established . In hTERT RPE 1 claudins were found only in internal vesicular like structures . Nonetheless claudins increased the expression of the mRNAs for a collection of RPE enriched proteins . Claudin 19 and claudin 3 had different effects on gene and protein expression indicating activation of overlapping but distinct signaling pathways . A major difference was the ability of claudin 19 to affect steady state levels of ADAM9 and tyrosinase in ARPE 19 . In conclusion claudins can increase the barrier function of a pre existing apical junctional complex but on its own it can not recruit tight junction proteins to form a complex | We expressed claudin 19 and claudin 3 in two human RPE cell lines that lack it ARPE 19 and hTERT RPE 1. The formation of tight junctions was accelerated in ARPE 19 but tight junctions did not form in hTERT RPE 1. There were distinct effects on gene expression even though there is no apical junctional complex in hTERT RPE 1. Despite increased mRNA claudin 19 suppressed the steady state levels of the proteins for. and. in ARPE 19. |
S0014483520304243 | Inherited retinal degenerative disorders such as retinitis pigmentosa and Usher syndrome are characterized by progressive death of photoreceptor cells . To restore vision to patients blinded by these diseases a stem cell based photoreceptor cell replacement strategy will likely be required . Although retinal stem cell differentiation protocols suitable for generating photoreceptor cells exist they often yield a rather heterogenous mixture of cell types . To enrich the donor cell population for one or a few cell types scientists have traditionally relied upon the use of antibody based selection approaches . However these strategies are quite labor intensive and require animal derived reagents and equipment that are not well suited to current good manufacturing practices . The purpose of this study was to develop and evaluate a microfluidic cell sorting device capable of exploiting the physical and mechanical differences between retinal cell types to enrich specific donor cell populations such as Retinal Pigment Epithelial cells and photoreceptor cells . Using this device we were able to separate a mixture of RPE and iPSC derived photoreceptor precursor cell lines into two substantially enriched fractions . The enrichment factor of the RPE fraction was 2 and that of the photoreceptor precursor cell fraction was 2.7 . Similarly when human retina obtained from 3 independent donors was dissociated and passed through the sorting device the heterogeneous mixture could be reliably sorted into RPE and photoreceptor cell rich fractions . In summary microfluidic cell sorting is a promising approach for antibody free enrichment of retinal cell populations . | Biomechanical analysis of ARPE 19 and human iPSC derived photoreceptor precursor cells. Microfluidic enrichment of human iPSC derived photoreceptor precursor cells. Label free microfluidic fractionation of human retinal cells to enrich primary photoreceptor cells. |
S0014483520304255 | In age related macular degeneration inflammatory events are presumed to contribute to disease development . A primary suspect of this contribution is the microglia the innate immune cell of the retina . In addition retinal pigment epithelium cells can be inflammatorily activated . In this study we investigate the effect of activated RPE cells on retinal microglia and on neuronal cells . RPE cells and microglia were harvested from porcine eyes . In addition a neuronal cell line of human origin was used . For inflammatory activation agonists of toll like receptors in different concentrations were used Pam2CSK4 Polyinosinic polycytidylic acid and lipopolysaccharid . Cell viability was investigated with an MTT assay . The secretion of cytokines was assessed in an ELISA and their expression in real time PCR . There was no effect of the agonists on cell viability in RPE cells . All agonists induced the secretion of IL 6 and IL 8 in RPE cells with the strongest effect induced by LPS . In microglia pro inflammatory stimulation increased the metabolic activity . All agonists induced the secretion of IL 1 IL 8 and TNF in microglia cells while in real time PCR LPS and Pam induced the expression of IL 6 IL 1 and iNOS . Direct stimulation of SHSY 5Y with the agonists induced only minor alterations of viability . Stimulated RPE cell supernatant reduced the secretion of TNF and IL 8 irrespective of the inducing agent in microglia cells . Additionally a slight induction of IL 1 was found in microglia treated with supernatant of RPE cells treated with Pam . In real time PCR the supernatant of RPE cells stimulated with LPS significantly reduced the expression of iNOS and IL 6 but not of IL 1 . Of note the expression of iNOS was also reduced by naive RPE cells . The treatment of the SHSY 5Y with supernatant of microglia previously treated with RPE conditioned medium significantly decreased SHSY 5Y viability with and without pro inflammatory treatment . In conclusion inflammatory activated RPE cells have a regulatory effect on the pro inflammatory activation of microglia stressing the importance of the interaction between these two retinal cell types . Microglia treated with RPE supernatant reduced viability of a neuronal cell line indicating a neurotoxic effect . | Toll like receptor activation does not impede cell viability in retinal pigment epithelial cells and microglia. Toll like receptor agonists induce IL 6 in RPE and IL 1 and TNF in microglia. IL 8 is induced in both cell types. The supernatant of activated RPE cells reduce the secretion of TNF and of IL 8 in microglia. The supernatant of RPE activated with LPS reduce the expression of IL 6 and the expression of iNOS in microglia cells. SHSY 5Y viability is reduced when treated with supernatant of microglia previously treated with RPE cells. |
S0014483520304267 | confocal microscopy allows the evaluation of the living human cornea at the cellular level . The non invasive nature of this technique longitudinal repeated examinations of the same tissue over time . Image analysis of two dimensional time lapse sequences of presumed immune cells with and without visible dendrites at the corneal sub basal nerve plexus in the eyes of healthy individuals was performed . We demonstrated evidence that cells without visible dendrites are highly dynamic and move rapidly in the axial directions . A number of dynamic cells were observed and measured from three eyes of different individuals . The total average displacement and trajectory speeds of three cells without visible dendrites was calculated to be 1.120.21 and 1.350.17 m per minute respectively . One cell with visible dendrites per cornea was also analysed . Tracking dendritic cell dynamics in vivo has the potential to significantly advance the understanding of the human immune adaptive and innate systems . The ability to observe and quantify migration rates of immune cells in vivo is likely to reveal previously unknown insights into corneal and general pathophysiology and may serve as an effective indicator of cellular responses to intervention therapies . | Corneal immune cell dynamics can be assessed in humans using in vivo confocal microscopy. In vivo confocal microscopy can be used for time lapse imaging by using corneal nerves junctions as landmarks. Corneal cells without visible dendrites are highly dynamic in their human natural niche. |
S0014483520304279 | Accumulation of lipofuscin deposits in the retinal pigment epithelium is one of the main events involved in age related macular degeneration and its increase together with RPE dysfunction blood retinal barrier disruption and photoreceptors death progressively leads to blindness . Lipofuscin is the main autofluorescent component of the retina and therapies to counteract its deposition are a main goal to be achieved since effective treatments have not yet been identified . Here we first investigated the spatio temporal pattern of AF deposits accumulation in the light damage model of age related macular degeneration . Afterward we tested the ability of cerium oxide nanoparticles a well known anti oxidant agent to counteract AF granules accumulation . The treatment was performed both before and after the induction of the degeneration . AF granules were quantified by confocal microscopy on whole mounted retinas . We demonstrated that the acute light damage increases the accumulation of AF deposits in the hot spot retina in terms of number of granules and percentage of occupied area with a peak 7 days after the exposure . Remarkably cerium oxide nanoparticles showed a strong efficacy in preventing the formation of AF deposits when they were injected 3 days before light exposure . Moreover when the treatment was performed 7 days after light exposure nanoceria activity was found to be effective also in reducing the amount of the AF granules still deposited up to 60 days . These important results represent the very first evidence about the ability of cerium oxide nanoparticles to counteract AF deposits accumulation in retinal degeneration laying the foundations for the development of a new therapy possibly targeting lipofuscin in AMD . | Acute light damage induces massive autofluorescence deposits accumulation in the rat retina. Preventive treatment with nanoceria inhibits autofluorescence deposits accumulation. Nanoceria promote removal of retinal autofluorescence deposits. |
S0014483520304371 | Tissue plasminogen activator has been shown to prevent steroid induced reduction in aqueous humor outflow facility via an upregulation in matrix metalloproteinase | Intraocular fibrinolytic pathway expression is unchanged in. mice. Outflow facility is not further reduced by steroids in. mice. Tissue plasminogen activator improves outflow facility in. mice. Tissue plasminogen activator enhances intraocular. expression in. mice. |
S0014483520304383 | Previously we developed TAT N24 as a synthetic cell permeable peptide inhibitor of p55PIK signaling and demonstrated its anti inflammatory effects . This study aimed to evaluate the potential of TAT N24 as a new agent for the treatment of ocular inflammatory diseases . The endotoxin induced uveitis model was established by intravitreal injection of lipopolysaccharide in BALB c mice and experimental autoimmune uveitis model was established by subcutaneous injection of a peptide spanning amino acid residues 161180 of interphotoreceptor retinoid binding protein with complete Freund s adjuvant in B10.RIII mice . TAT N24 was topically administered in EIU model and intraperitoneally administered in EAU model . The severity levels of uveitis were assessed by clinical and histopathological scores . The mRNA levels of inflammatory cytokines in iris ciliary body and retina were analyzed by reverse transcription quantitative polymerase chain reaction . The protein levels of inflammatory factors were determined by ELISA or Western blotting . The results showed that TAT N24 alleviated clinical signs decreased inflammatory cell infiltration and the expression of inflammatory cytokines in both EIU and EAU models . Furthermore protein levels of tumor necrosis factor alpha interleukin 1 and interleukin 6 in aqueous humor and mRNA and protein levels of NF B p65 in the ICB significantly decreased in EIU model . In EAU model TAT N24 application induced a significant decrease of IFN gamma and interleukin 17 in the retina which were secreted by Th1 and Th17cells respectively . In conclusion TAT N24 suppressed intraocular inflammation in both EIU and EAU models and the anti inflammatory effects were mediated by suppressing the expression of inflammatory cytokines by PI3K NF B signaling pathway . TAT N24 could be potential candidate for the treatment of ocular inflammatory diseases . | TAT N24 is a synthetic cell permeable peptide inhibitor of p55PIK signaling. Topical administration of TAT N24 alleviated acute ocular inflammation in EIU model. Intraperitoneal injection of TAT N24 alleviated chronic ocular inflammation in EAU model. TAT N24 alleviated ocular inflammation by suppressing the production of inflammatory cytokines. Anti inflammatory effects of TAT N24 were mediated by inhibiting NF B activation. |
S0014483520304395 | Homeostasis of the corneal epithelium is ultimately maintained by stem cells that reside in a specialized microenvironment within the corneal limbus termed palisades of Vogt . This limbal niche nourishes protects and regulates quiescence self renewal and fate decision of limbal epithelial stem progenitor cells toward corneal epithelial differentiation . This review focuses on our current understanding of the mechanism by which limbal niche cells regulate the aforementioned functions of LEPCs . Based on our discovery and characterization of a unique extracellular matrix termed HC HA PTX3 hyaluronan pentraxin 3 complex denotes covalent linkage denotes non covalent binding in the birth tissue i.e . amniotic membrane and umbilical cord we put forth a new paradigm that HC HA PTX3 serves as a surrogate matrix niche by maintaining the in vivo nuclear Pax6 neural crest progenitor phenotype to support quiescence and self renewal but prevent corneal fate decision of LEPCs . This new paradigm helps explain how limbal stem cell deficiency develops in aniridia due to Pax6 haplotype deficiency and further explains why transplantation of HC HA PTX3 containing amniotic membrane prevents LSCD in acute chemical burns and Stevens Johnson syndrome augments the success of autologous LEPCs transplantation in patients suffering from partial or total LSCD and assists ex vivo expansion of a graft containing LEPCs . We thus envisage that this new paradigm based on regenerative matrix HC HA PTX3 as a surrogate niche can set a new standard for regenerative medicine in and beyond ophthalmology . | Salient features of limbal niche cells. HC HA PTX3 found in amniotic membrane and umbilical cord may serve as a surrogate matrix niche.for regenerative medicine in ophthalmology and beyond. |
S0014483520304401 | Myopia is a prevalent eye disorder especially among children and adolescents in eastern Asian countries . Multiple measures have already been taken to prevent and treat myopia including atropine and dopamine . However the serum metabolic picture of myopia has not yet been studied as a whole and remains largely unclear . In this paper a prospective and panoramic study was carried out to find out the whole serum metabolomic and lipidomic picture of myopia . With untargeted mass spectrometry myopia among 211 children and adolescents was studied . The MS features were first grouped across the samples . Then compound annotation was carried out based on these features . Finally the metabolite features were mapped to pathways whose biological functions in myopia were studied and discussed . A total of 275 metabolite features were derived from 92 aligned MS peak groups with significant fold changes and then mapped to 33 pathways . By a comprehensive consideration of significance fold change importance score and appearance in different omics 9 pathways were selected and their biological functions were further analyzed . Among these selected pathways 5 pathways were related with oxidative stress a validated phenomenon during myopia development while 5 pathways were related with dopamine receptor D2 whose molecular function in myopia treatment is not fully understood . A total of 177 metabolite features from 45 peak groups were related with the studied pathways . This prospective study shed light on the whole picture of metabolomic mechanism underlying myopia and provided guidance to further elucidation of compounds and pathways in this whole picture . | Serological metabolic lipid changes discovered in myopic children and adolescents. Untargeted mass spectrometry revealed changes in 275 features and 33 pathways. Enriched pathways related with oxidative stress and dopamine receptor D2. |
S0014483520304413 | Mller cells represent a key element for the metabolic and functional regulation of the vertebrate retina . The aim of the present study was to test the feasibility of a new method for the in vivo detection and quantification of extrafoveal MC in human retina . We developed a new approach to isolate and analyse extrafoveal MC in vivo starting from structural optical coherence tomography data . Our pilot investigation was based on the optical properties of MC which are known to not interfere with the light reaching the outer retinal structures . We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed 42 000 9mm | We developed a non invasive quantitative approach to detect and quantify extrafoveal Mller cells in vivo in human retina. The Mller cells imaging morphology disclosed a good matching with histologic analysis. The macular Mller cell density was of 42 000 9mm |
S0014483520304425 | Retinoblastoma is a childhood eye tumor caused by RB1 mutation . Though diagnosing RB is easier prognosticating RB is limited to examining the patient under anesthesia and imaging technique . The aim of the study is to find exosomal miRNA biomarkers to prognosticate RB . Exosomes were isolated from one control MIO M1 and two RB cell lines WERI Rb 1 and NCC RbC 51 . Small RNA sequencing was performed on exosomal miRNA isolated from the three cell lines . miRNAs specific to each cell line were shortlisted . A total of 243 606 and 400 miRNAs were identified in MIO M1 WERI Rb 1 and NCC RbC 51cell lines respectively . Nine miRNAs were shortlisted based on adjusted p value and literature MIO M1 specific WERI RB 1 specific NCC RbC 51 specific and miRNAs common to both RB cell lines were chosen . Validation was done using specific Taqman miRNA assays.miRNA validation was carried out on cell lines cell line derived exosomes primary RB tissues and exosomes isolated from serum of the RB patients . Validation of the miRNAs in cell lines and exosomes derived from the cell lines confirmed the sequencing data . However only 2 miRNAs hsa miR 301b 3p and hsa miR 216b 5p were upregulated in the primary RB tissues . None of the miRNAs had significant expression in the serum exosomes of RB patients . Therefore serum exosomal miRNA may not be ideal for prognosticating RB.Further research on other body fluids like CSF and vitreous could serve as potential source for biomarkers for prognosticating RB . | Prognosticating RB is limited to examining the patient under anesthesia and imaging technique. Exosomes from the two RB cell lines and the Muller glial cell line were subjected to small RNA sequencing. A total of 9 miRNAs were validated in the cell lines and cell line derived exosomes. Two of the highly expressed RB specific miRNAs were significantly upregulated in 17 primary RB tissues. Validation in serum exosomes did not yield any significant results. hsa miR 301b 3p showed expression in vitreous. |
S0014483520304437 | Age related cataract is the leading cause of visual impairment or even blindness among the aged population globally . Long non coding RNA has been proven to be the potential regulator of ARC . The latest study reveals that maternally expressed gene 3 promotes the apoptosis and inhibits the proliferation of multiple cancer cells . However the expression and role of MEG3 in ARC are unclear . In this study we investigated the effects of MEG3 in ARC and explored the regulatory mechanisms underlying these effects . We observed that MEG3 expression was up regulated in the age related cortical cataract lens capsules and positively correlated with the histological degree of ARCC . The pro apoptosis protein active caspase 3 and Bax increased in the anterior lens capsules of ARCC tissue while the anti apoptotic protein Bcl 2 decreased compared to normal lens . Knockdown of MEG3 increased the viability and inhibited the apoptosis of LECs upon the oxidative stress induced by H | MEG3 expression was up regulated in the age related cortical cataract ARCC lens capsules and positively correlated with the histological degree of ARCC. TP53INP1 knockdown alleviated H. induced lens turbidity. MEG3 promoted ARC progression by up regulating TP53INP1 expression through suppressing miR 223 and promoting P53 expression. |
S0014483520304449 | A significant proportion of research on the visual system focuses on general principles that apply to samples and or populations . Many questions however are more suited to the specific characteristics of an individual . The visual system like most systems of the body is extremely variable with respect to function and susceptibility to disease . Understanding this variation is an important avenue to better measurement disease prevention and treatment . | All things equal even young healthy adults show large individual variation in visual parameters and function. For example. Peak macular pigment and lens optical density vary by over a factor of ten. Photostress recovery times vary by over a factor of eight. Visual range how far one can see varies by about 30 despite equal refractive state. Intraocular scatter with its related glare issues varies over a two log unit range. |
S0014483520304450 | The study aimed to evaluate the intraocular pharmacokinetics and efficacy of aflibercept after subconjunctival injection in animal models for treating choroidal neovascularization associated with Age Related Macular Degeneration . New Zealand albino rabbits received aflibercept in one eye and the other eye was used as control . At 7 14 21 and 28 days the animals were sacrificed to dissect the ocular tissues and serum was collected at 1hr 3h 1 7 14 21 and 28 days . The concentration of aflibercept in various ocular tissues and serum were measured using the immunoassay technique . The concentration maximum C | A delivery system that could release aflibercept in the subconjunctival space for a longer period as well to protect it from the conjunctival clearance to avoid increased systemic exposure would be highly beneficial. The subconjunctival aflibercept could be a less invasive route for treating chorioretinal diseases. |
S0014483520304462 | Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head . Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal . Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure . Following the same general approach of previous parametric sensitivity studies we created nonlinear generic finite element models of a posterior pole with various combinations of radial and circumferential fibers at an IOP of 0mmHg . We then simulated the effects of normal and elevated IOP levels . We monitored four IOP induced geometric changes peripapillary sclera stretch scleral canal displacement lamina cribrosa displacement and scleral canal expansion . In addition we examined the radial and through thickness strains within the ONH tissues . Our models predicted that 1 radial fibers reduced the posterior displacement of the lamina especially at elevated IOP 2 radial fibers reduced IOP induced radial strain within the peripapillary sclera and retinal tissue and 3 a combination of radial and circumferential fibers maintained strains within the ONH at a level similar to those conferred by circumferential fibers alone . In conclusion radial fibers provide support for the posterior globe additional to that provided by circumferential fibers . Most importantly a combination of both fiber families can better protect ONH tissues from excessive IOP induced deformation than either alone . | Radial fibers reduce lamina cribrosa displacement especially at elevated IOP. Radial fibers reduce the maximum tension in peripapillary sclera and retinal tissues. Radial and circumferential fibers together protect the ONH better than either alone. |
S0014483520304474 | Meibomian glands that are embedded in tarsal plates of human eyelids and sebaceous glands found in the skin including that of eyelids are two related types of holocrine glands that produce lipid rich secretions called meibum and sebum . Pervasive ocular disorders such as Meibomian gland dysfunction and dry eye have been linked to changes in the lipid composition of meibum . However in most described cases the changes were either small or random or insufficiently characterized on the molecular level . Here we present results of comprehensive lipidomic analyses of meibum tears and sebum of a patient whose secretions were highly abnormal . The lipidomes were characterized on the level of individual lipid species using ultra high performance liquid chromatography and high resolution mass spectrometry . The major differences between the AMTS patient and normal age and gender matched subjects included among others severely diminished pools of normal meibomian lipids such as wax esters and cholesteryl esters in meibum and tears a 2x increase in total cholesteryl esters to wax esters ratio their skewed molecular profiles a 3x increase in free cholesterol to cholesteryl esters ratio and most importantly a 20x to 30x increase in the triglicerides fraction over the norm . Sebum of the AMTS patient was also highly abnormal lacking major wax esters . Notably the routine blood lipid panel test of the AMTS patient showed no abnormalities . The data imply that the AMTS patient had a severe previously unreported metabolic disorder that affected meibogenesis in Meibomian glands and sebogenesis in sebaceous glands . This is to the best of our knowledge a first observation of the condition that we have termed High Triglycerides Low Waxes syndrome . | A severe metabolic disorder affects lipid homeostasis in Meibomian glands and tears. Triglycerides TAG were 20x to 30x over the normal levels. The increase in TAG led to a decline in wax esters WE and cholesteryl esters CE . Free cholesterol in abnormal meibum was increased 3x over the normal levels. The disorder also affected sebaceous lipids specifically lowering their WE TAG ratio. |
S0014483520304486 | To determine whether the CD27 CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27 CD70 pathway by anti CD70 antibody on corneal allograft survival . Orthotopic penetrating keratoplasty was performed using C57BL 6 donor grafts and BALB c recipients . Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry . Corneal transplant recipients received intraperitoneal injection of anti CD70 antibody or control rat IgG . Alloreactivity was measured by mixed lymphoid reaction in recipients administered control rat IgG and those administered anti CD70 antibody . Corneal expression of IFN and IL 12 was also examined in both groups . Graft opacity was assessed over an 8 week period and graft survival was evaluated using Kaplan Meier survival curves . Proportion of CD4 CD4 The CD27 CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells . Anti CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27 CD70 pathway blockade on corneal allograft rejection . | CD27 and CD70 were expressed in the rejected cornea. Anti CD70 antibody reduced allogeneic T cell reaction and prolonged corneal allograft survival. |
S0014483520304498 | Germinal peptide is being developed to treat corneal injuries . The purpose of this study was to investigate its effect on corneal epithelial cells | We studied the effect of germinal peptide GP on healing of alkali eye damage. Twenty and 40g ml GP significantly alleviated corneal opacity and edema. At 21d corneal neovascularization epithelial layers and inflammation were lower. GP increased rabbit corneal epithelial cell migration. GP may provide a novel topical approach to corneal wound healing in the clinic. |
S0014483520304504 | Due to their very poor proliferative capacity the dysfunction of corneal endothelial cells can sometimes lead to incurable eye diseases that require corneal transplantation . Although many studies have been performed to reconstruct corneal endothelial cells corneal transplantation is still considered to be the established approach . In this study we developed bio engineered Descemet stripping endothelial layers using porcine cornea and induced pluripotent stem cell derived corneal endothelial cells . First we optimized a protocol to prepare an ultra thin and decellularized Descemet stripping scaffold from porcine cornea . Our DS layers show over 90 transparency compared to the control . Porcine derived cells and xenogenic antigens disappeared whereas the collagen matrix remained in the graft . Next corneal endothelial cell lines or iCECs were seeded on the decellularized DS graft and cultured for 7 days . The drying method reduced graft rolling and edema and increased transparency during culture . The reseeded cells were evenly distributed over the graft and most of the cells survived . Although future clinical studies are warranted engineered DSE tissues using xenogenic tissues and stem cells will be useful tools for the treatment of incurable corneal diseases . | We optimized the decellularization protocols for ultra thin and transparent Descemet stripping grafts from porcine eyes. We optimized the recellularization to produce a clear and homogeneously reseeded Descemet stripped endothelial tissue. The stem cell derived corneal endothelial cells were evenly spread and attached on the engineered endothelial tissue. The engineered Descemet stripping endothelial grafts using stem cells will be promising for the corneal diseases. |
S0014483520304516 | Recent studies have shown that lactate coupled water flux is the underlying mechanism of the corneal endothelial pump which is highly dependent on the presence of bicarbonate . In this study we test the hypothesis that the increased intracellular pH pH | Effect of Bicarbonate free vs Bicarbonate Rich Ringer on Corneal Endothelial Lactate Production. Increased pHi in Bicarbonate. Intracellular Lactate Measurement by Laconic. Bicarbonate Rich Ringer Accelerates Lactate Production. |
S0014483520304528 | A sight threatening pterygium is a common ocular surface disorders identified by fibrovascular growth of the cornea and induced by variety of stress factors like ultraviolet exposure . However the genes involved in the etiopathogenesis of this disease is not well studied . Herein we identified the gene expression pattern of pterygium and examined the expression of pterygium related genes in UV B induced human primary cultured corneal epithelial cells telomerase immortalized human corneal epithelial primary conjunctival fibroblast and primary pterygium fibroblast cells . A careful analysis revealed that the expression of 10 genes was significantly modulated . Keratin 24 | Expressions of KRT24 and MMP 9 are related to the pterygium progression. Extracellular matrix cell migration and angiogenesis induce the pterygium. UVB irradiation induced the upregulation of. and. 9 mRNAs. KRT24 was not expressed in human fibroblast cells. |
S001448352030453X | Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy . Choroidal inflammatory changes in diabetes have been reported and | Early Type 1 diabetes alters pericyte cells distribution in the inner choroid. The expression of VEGR2 decreases in the retina. Proliferation and reactivity of microglia occurs in the choroid and the retina. Choroidal thickness and vascular density do not change in early Type 1 diabetes. |
S0014483520304541 | Connectomics has demonstrated that synaptic networks and their topologies are precise and directly correlate with physiology and behavior . The next extension of connectomics is pathoconnectomics to map neural network synaptology and circuit topologies corrupted by neurological disease in order to identify robust targets for therapeutics . In this report we characterize a pathoconnectome of early retinal degeneration . This pathoconnectome was generated using serial section transmission electron microscopy to achieve an ultrastructural connectome with 2.18nm px resolution for accurate identification of all chemical and gap junctional synapses . We observe aberrant connectivity in the rod network pathway and novel synaptic connections deriving from neurite sprouting . These observations reveal principles of neuron responses to the loss of network components and can be extended to other neurodegenerative diseases . | The first ultrastructural pathoconnectome of a degenerating neural network. Rewiring of retinal networks occurs prior to complete loss of afferent input. Neurites extended by retinal neurons synapse with expected and novel partners. Novel gap junctions are formed by rod bipolar cells early retinal degeneration. |
S0014483520304553 | Lowering intraocular pressure is the most effective treatment of glaucoma however most of the current available glaucoma drugs target a single molecule . MicroRNAs are noncoding RNAs that target a network of molecules . This study aims to investigate the role of miR 21 5p in regulating IOP and the mechanism of function . miR 21 5p mimics was topically applied to C57 BL6 mouse eyes which significantly increased miR 21 5p expression in the conventional outflow tissue and reduced IOP by a maximum of 17.77 at 24h after treatment . The conventional outflow facility measured by ex vivo moue eye perfusion of miR 21 5p was significantly increased by 60.14 . Moreover miR 21 5p overexpression significantly reduced the transendothelial electrical resistance in porcine angular aqueous plexus cells . Transcriptome analysis and further quantification by Western blot and PCR revealed that SMAD7 and FGF18 might be the downstream target of miR 21 5p in regulating aqueous humor outflow . The predicted functional pathways PTEN eNOS RhoB pMLC and TIMP3 MMP9 were significantly altered after miR 21 5p transfection . Dual luciferase assay verified the direct targets of miR 21 5p . In conclusion miR 21 5p seems to regulate IOP by modulating multiple genes that are associated with aqueous humor outflow including genes those regulating cell adhesion cytoskeletal dynamics and extracellular matrix turnover . Thus miR 21 5p represents a new therapeutic strategy for glaucoma and a viable alternative to existing multidrug regimens . | The microRNA miR 21 5p regulates intraocular pressure through targeting conventional outflow pathway. It alters cell junction adhesion cytoskeletal dynamics and extracellular matrix turnover in conventional outflow cells. miR 21 5p potentially represents a new therapeutic strategy for glaucoma and a alternative to existing multidrug regimens. |
S0014483520304565 | Retinopathy of prematurity is a potentially blinding condition caused by disruption of retinal vascularization and metabolism . This study aims to identify altered metabolites from plasma in patients with treatment requiring ROP compared with controls . An untargeted metabolomics analysis was performed to reveal the metabolomic profiles of the plasma between TR ROP patients | A metabolomics analysis was performed in plasma of treatment requiring ROP. Altered plasma metabolites could be considered as potential biomarkers of treatment requiring ROP patients. Protein digestion and absorption and aminoacyl tRNA biosynthesis were the most enriched pathways. |
S0014483520304577 | Ultraviolet A light based photoactivation of riboflavin to induce corneal crosslinking and mechanical stiffening is now a well known treatment for corneal ectasia and Keratoconus that is being used in a topographically guided photorefractive intrastromal CXL procedure to treat low degrees of refractive errors . Alternative approaches for non invasive treatment of refractive errors have also been proposed that use femtosecond lasers that provide much faster more precise and safer results than UVA CXL . One such treatment nonlinear optical crosslinking has been able to replicate the effects of UVA CXL while producing a smaller area of cellular damage and requiring a shorter procedure time . Unlike UVA CXL the treatment volume of NLO CXL only occurs within the focal volume of the laser which can be placed at any depth and scanned into any pattern for true topographically guided refractive correction . This review presents our experience with using FS lasers to photoactivate Rf and perform highly controlled corneal CXL that leads to mechanical stiffening and changes in corneal shape . | NLO CXL produces a detectable increase in mechanical stiffness in collagen hydrogels. Rapid NLO CXL using an enlarged focal volume produced increased mechanical stiffness and CAF intensity in ex vivo rabbit eyes. A custom built NLO CXL device was able to deliver an adjustable focal volume and produce crosslinking comparable to UVA CXL. Amplified pulses are capable of producing NLO CXL with zero pulse overlap while staying within the ANSI power limits. Epithelial microchannels enable higher riboflavin penetration with less damage than BAK for transepithelial crosslinking. |
S0014483520304589 | Prion diseases are invariably fatal neurodegenerative disorders that have gained much publicity due to their transmissible nature . Sporadic Creutzfeldt Jakob disease is the most common human prion disorder with an incidence of 1 in a million . Inherited prion disorders are relatively rare and associated with mutations in the prion protein gene . More than 50 different point mutations deletions and insertions have been identified so far . Most are autosomal dominant and fully penetrant . Prion disorders also occur in animals and are of major concern because of the potential for spreading to humans . The principal pathogenic event underlying all prion disorders is a change in the conformation of prion protein PrP | Prion protein PrP. is expressed in the anterior posterior segment of the eye. Absence of PrP. promotes endothelial to mesenchymal transition in TM cells. PrP. helps to maintain iron homeostasis in the anterior segment. Anterior segment maintains iron homeostasis independent of the retina. TGF2 and hepcidin form a positive feed forward loop fueled by iron catalyzed ROS. |
S0014483520304590 | Mesenchymal stromal cells with progenitor cell and immunological properties have been cultivated from numerous vascularized tissues including bone marrow adipose tissue and the corneal limbus of the eye . After observing mesenchymal cells as contaminants in primary cultures of vascular endothelial cells derived from the choroidal tunic of the human eye we investigated whether the choroid might also provide a source of cultured MSC . Moreover we examined the effect of the choroidal stromal cells on the proliferation of freshly isolated choroidal vascular endothelial cells | There is a resident population of mesenchymal stromal cells in the human choroid. Cultures established from the human choroidal stroma displayed a phenotype consistent with the accepted definition for MSC including the capacity for mesenchymal differentiation. Growth arrested choroidal MSC inhibit the proliferation of choroidal derived vascular endothelial cells in primary culture. |
S0014483520304607 | Mechanical insult induced by intraocular pressure is likely a driving force in the disease process of glaucoma . This study aimed to evaluate regional displacements in human optic nerve head and peripapillary tissue in response to acute IOP elevations and their correlations with morphological characteristics of the posterior eye . Cross sectional images of the ONH and PPT in 14 globes of 14 human donors were acquired with high frequency ultrasound during whole globe inflation from 5 to 30mm Hg . High frequency ultrasound has a spatial resolution of tens of micrometers and is capable of imaging through the ONH and PPT thickness . Tissue displacements were calculated using a correlation based speckle tracking algorithm for a dense matrix of kernels covering the 2D imaging plane . The ONH was manually segmented in the ultrasound B mode images acquired at 5mmHg based on echogenicity . The lamina cribrosa boundaries were visible in eight of the fourteen eyes and the LC region was segmented using a semi automated superpixel based method . The ONH had larger radial displacement than the PPT in all tested eyes and the difference increased with increasing IOP . A significant negative correlation was found between ONH PPT displacement difference and PPT thickness while no significant correlations were found between ONH PPT displacement difference and other morphological parameters including PPT radius of curvature scleral canal size LC thickness and anterior LC surface depth . Within the ONH the radial displacement decreased in the region anterior to and across LC but not in the region posterior to LC . Finite element models using simplified geometry and material properties confirmed the role of LC in reducing the overall ONH radial displacements but did not predict the displacement gradient change observed experimentally . These results suggested that a thinner PPT may be associated with a larger relative posterior motion of the ONH with respect to the surrounding PPT and the LC may play a major role in preventing excessive posterior displacement of ONH during acute IOP elevations . | ONH PPT displacement difference at IOP elevation was negatively correlated with PPT thickness. Radial displacement decreased in the ONH region anterior to and across LC but plateaued in the region posterior to LC. LC may reduce the posterior displacement of ONH during IOP elevation. |
S0014483520304619 | The involvement of leukocytes in the pathophysiology of DR has mostly examined the role of monocytes and neutrophils with little emphasis on other immune cell types . In this study we determined the systemic alterations in T cell subsets myeloid cell types NK cells and NKT cells in the streptozotocin mouse model of diabetic retinopathy and the role of NKT cells on retinal leukostasis and permeability changes . C57BL 6J mice were made diabetic with 60mg kg dose of STZ given for 5 days . Flow cytometry assay measured the frequency of leukocyte subsets in the peripheral blood spleen and bone marrow of STZ and vehicle treated C57BL 6J mice . Our results showed an increased proportion of memory CD8 T cells and interferon gamma secreting CD8 T cells in the bone marrow of STZ treated compared to control mice . Subsequently increased production of inflammatory monocytes in the bone marrow and an enhanced frequency of CD11b cells in the diabetic retina were seen in STZ treated compared to control mice . The diabetic mice also exhibited a decrease in total NKT and CD4 NKT cells . A monoclonal antibody based approach depleted NKT cells from STZ treated mice followed by measurements of retinal vascular permeability and leukostasis . The depletion of NKT cells in STZ treated mice resulted in a significant increase in vascular permeability in the retinal tissue . Together our results strongly imply the involvement of NKT cells in regulating the pathophysiology of the diabetic retina . | Retinal inflammation is involved in the pathogenesis of diabetic retinopathy. In diabetic retinopathy NKT cell frequency decreases in the peripheral blood. IFN secreting CD8 T cells increases in the bone marrow of diabetic mice. Loss of NKT cells enhances vascular permeability and leukostasis in diabetic retina. |
S0014483520304620 | Single cell RNA sequencing has revolutionized ocular gene expression studies . This technology has enabled researchers to identify expression signatures for rare cell types and characterize how gene expression changes across biological conditions such as topographic region or disease status . However sharing single cell RNA sequencing results remains a major obstacle particular for individuals without a computational background . To address these limitations we developed Spectacle an interactive web based resource for exploring previously published single cell RNA sequencing data from ocular studies . Spectacle is powered by a locally developed R package cellcuratoR which utilizes the Shiny framework in R to generate interactive visualizations for single cell expression data . Spectacle contains five pre processed ocular single cell RNA sequencing data sets and is accessible via the web at OcularGeneExpression.org singlecell . With Spectacle users can interactively identify which cell types express a gene of interest detect transcriptomic subpopulations within a cell type and perform highly flexible differential expression analyses . The freely available Spectacle system reduces the bioinformatic barrier for interacting with rich single cell RNA sequencing studies from ocular tissues making it easy to quickly identify cell types that express a gene of interest . | Spectacle is a resource for exploring ocular single cell RNA sequencing datasets. Spectacle includes five datasets from the retina RPE and choroid. Spectacle facilitates interactive expression analyses on pre classified cell types. Spectacle is freely available at OcularGeneExpression.org singlecell. |
S0014483520304632 | We had previously found that M to L cone abundancy ratios in the chicken retina are correlated with vitreous chamber depth and refractive state in chickens eyes when they have normal visual exposure but not when they develop deprivation myopia . The finding suggests an interaction between cone abundancies and emmetropization . In the current study we analyzed how stable this correlation was against changes in environmental variables and strain differences . We found that the correlation was preserved in two chicken strains as long as they were raised in the laboratory facilities and not in the animal facilities of the institute . To determine the reasons for this difference spectral and temporal lighting parameters were better adjusted in both places whereas temperature humidity food diurnal lighting cycles and illuminance were already matched . It was also verified that both strains of chickens had the same cone opsin amino acid sequences . The correlation between M to L cone abundancy and ocular biometry is highly susceptible to changes in environmental variables . Yet undetermined differences in lighting parameters were the most likely reasons . Other striking findings were that green cone opsin mRNA expression was downregulated when deprivation myopia developed . Similarly red opsin mRNA was downregulated when chicks wore red spectacles which made them more hyperopic . In summary our experiments show that photoreceptor abundancies opsin expression and the responses to deprivation and therefore emmetropization are surprisingly dependent on subtle differences in lighting parameters . | The correlation of M to L cone ratios with axial length eyes was highly susceptible to changes in lighting parameters. Cone opsin expression was changed both by deprivation myopia and spectral filtering. Lighting parameters had a larger effect on opsins and deprivation myopia than expected. |
S0014483520304644 | Keratins are the forming units of intermediate filaments that provide mechanical support and formation of desmosomes between cells and hemi desmosomes with basement membranes for epithelium integrity . Keratin IF are polymers of obligate heterodimer consisting one type I keratin and one type II keratin molecules . There are 54 functional keratin genes in human genome which are classified into three major groups i.e . epithelial keratins hair follicle cell specific epithelial keratins and hair keratins . Their expression is cell type specific and developmentally regulated . Corneal epithelium expresses a subgroup of keratins similar to those of epidermal epithelium . Limbal basal stem cells express K5 K14 and K8 K18 and K8 K19 IF suggesting that there probably are two populations of limbal stem cells . In human LSCs at limbal basal layer can directly stratify and differentiate to limbal suprabasal cells that express K3 K12 IF or centripetally migrate then differentiate to corneal basal transient amplifying cells that co express both K3 K12 and K5 K14 prior to moving upward and assuming suprabasal cells phenotype of only K3 K12 expression that signifies corneal type epithelium differentiation . In rodent the differentiated cornea epithelial cells express K5 K12 in lieu of K3 K12 because K3 allele exists as a pseudogene and does not encode a functional K3 protein . The basal corneal cells of new born mice originate from surface ectoderm during embryonic development slowly commit to differentiation of becoming TAC co expressing K5 K12 and K5 K14 IF . However the centripetal migration may still occur at a slower rate in young mice which is accelerated during wound healing . In this review we will discuss and compare the corneaspecific keratins expression patterns between corneal and epidermal epithelial cells during mouse development and between human and mouse during development and homeostasis in adult and pathology caused by a mutation of keratins . | K3 K12 IF is the characteristics of cornea type epithelium differentiation in human. Rodent. allele is a pseudogene thus K5 K12 IF signified the murine corneal type epithelium differentiation. There are two populations of limbal stem cells that express K5 K14 or K8 K18 K19 IF. Missense keratin mutation is autosomal dominant nonsense keratin mutation is autosomal recessive. |
S0014483520304656 | Claudin 3 an integral component of tight junction has recently been shown to be expressed in retinal ganglion cells retinal pigment cells and retinal vascular endothelial cells . However the role of claudin 3 in the development of the neural retina and its vessels remains undefined . This study aimed to investigate the role of zebrafish claudin h the closest ortholog of mouse and human claudin 3 in the development of the neural retina and its vessels . Cldnh levels in green fluorescent protein transgenic zebrafish were genetically manipulated by cldnh morpholino oligonucleotide and cldnh mRNA to investigate gene function . The expression of cldnh was analyzed using polymerase chain reaction and immunofluorescence staining . The altered morphological cellular and molecular events in the cldnh MO morphant eyes were detected using hematoxylin eosin staining fluorescent dye injection confocal in vivo imaging BrdU labeling TUNEL assay RNA sequencing and Western blot . We demonstrated that the cldnh protein was expressed in the neural retina and the hyaloid vessel which is the predecessor of the retinal vessel in zebrafish . Cldnh knockdown delayed lamination of the neural retina and reduced its thickness which might be associated with the downregulation of the retinal development related genes of atoh7 pcdh17 crx neurod1 insm1a sox9b and cdh11 and the upregulation of the cell cycle and apoptosis associated genes of tp53 cdkn1a and casp8 . Cldnh knockdown also reduced the density and interrupted the lumenization of the hyaloid vessels which might be owing to the downregulation of the vessel formation related genes of hlx1 and myl7 . In conclusion cldnh was required for the normal development of the neural retina and its vessels in zebrafish providing a basis for elucidating its role in the pathogenesis of retinal vascular or inflammatory diseases . | Claudin h is required for normal development of neural retina and its vessels. Claudin h affects the density and the lumenization of the hyaloid vessels. Claudin h affects the lamination and the thickness of the neural retina. Claudin h affects the expression of atoh7 pcdh17 crx neurod1 insm1a and sox9b. Claudin h affects the expression of hlx1 and myl7. |
S0014483520304668 | The processes involved in neurodevelopment and aging have not yet been fully discovered . This is especially challenging in premorbid or borderline situations of neurodegenerative diseases such as Alzheimer s or glaucoma . The retina as part of the central nervous system can be considered the easiest and most accessible neural structure that can be analyzed using non invasive methods . Animal studies of neuroretinal tissue in situations of health and under controlled conditions allow the earliest sex and aging induced changes to be analyzed so as to differentiate them from the first signs occurring in manifested disease . This study evaluates differences by age and sex based on intraocular pressure and neuroretinal function and structure in healthy young and adult rats before decline due to senescence . For this purpose eighty five healthy LongEvans rats were analyzed in this 6 month longitudinal study running from childhood to adulthood . IOP was measured by tonometer neuroretinal function was recorded by flash scotopic and light adapted photopic negative response electroretinography at 4 16 and 28 weeks of age and structure was evaluated by | Studies in healthy animals are essential to differentiate from premorbid situations. This study first demonstrates sex and age related influence in healthy rat retina. Different patterns of neuronal development and degeneration by sex. Neuroretinal degeneration by sex is detected from adulthood in Long Evans rat. Male show early neurodegeneration so estrogens might have retinal protective role. |
S001448352030467X | To determine the roles of secretory phospholipase A2 IIa samples and tears were collected from patients with mild to severe non Sjogren s dry eye disease and normal controls . The IC samples were analyzed for transcription of sPLA Transcription of sPLA2 IIa was significantly increased in severe DED patients as compared to those of mild DED patients and normal controls . The transcription of inflammatory cytokines chemokines and matrix metalloproteinase 9 were simultaneously increased in the same IC samples of DED . Concentrations of IL 6 and IL 8 in tears were significantly higher in DED patients than those of the controls and positively correlated to DED severity scores . On the other hand IL 2 IL 4 IL 10 IL 12 and IFN were significantly lower in DED patients than those in the controls and inversely correlated to DEWS scores . Single treatment of sPLA2 IIa IL 1 or TNF of HCjE cells induced minimal to no PGE2 production . When sPLA2 IIa was added to HCjE cells that were pre treated with pro inflammatory cytokines significant stimulation of PGE2 production was observed concurrent with the extensive transcriptional changes of many inflammatory cytokines chemokines and their receptors . sPLA | sPLA2 IIa is upregulated in tears and ocular surface cells of DED patients. Upregulation is correlated with signs symptoms and other inflammatory biomarkers. sPLA2 IIa triggers more PGE2 release in compromised conjunctival epithelia cultures. sPLA2 IIa changes transcription of many inflammatory cytokines and chemokines. sPLA. IIa amplifies the ocular surface inflammation especially when is compromised |
S0014483520304681 | Previously calcitriol has been demonstrated as a potential therapeutic agent for dry eye whilst its role on corneal epithelium death remains unclear . This study aims to investigate the relationship between apoptosis and autophagy on dry eye related scenario as well as the effect of calcitriol and its potential mechanism . | Autophagy is highly activated in dry eye model. and. Autophagy plays a protective role in corneal epithelial cells against dry eye related apoptosis. Autophagy flux augmented by calcitriol further protects cornea epithelial cells from apoptosis. Vitamin D Receptor pathway correlates to the therapeutic effect of calcitriol. |
S0014483520304693 | The main purpose of this study is to evaluate the diagnostic role of Toll like receptors 2 and 4 expression in corneal and conjunctival epithelial cells of eyes with pellucid marginal degeneration compared to keratoconus patients and control subjects . A prospective case control study in 29 PMD eyes 109KC eyes and 72 healthy eyes was done . All participants were subjected to a clinical topographic aberrometric and tomographic exam with extraction of corneal and conjunctival epithelial cells through scraping . The TLR2 and TLR4 expression was measured with flow cytometry . Receiver operating characteristic curve analysis was used to determine the most appropriate cutoff point for predicting the risk of PMD and KC . Correlations between TLR2 TLR4 expression and the severity of PMD KC were evaluated . A TLRs follow up review was made 194 months after to the first review . As result mean expression of TLR2 and TLR4 in both corneal and conjunctival epithelial cells was significantly higher in eyes with corneal ectasia than in control eyes . Conjunctival TLR4 expression showed the highest capacity to diagnose the existence of PMD after adjusting by eye rubbing and steeper corneal meridian . Moreover we found an association between the TLR2 TLR4 overexpression with the severity of the PMD and KC measured by corneal topographic aberrometric and tomographic quantitative parameters . Differences on TLR2 TLR4 expression between study groups were maintained during the follow up period . In conclusion the TLR2 TLR4 overexpression in corneal and conjunctival epithelial cells of PMD and KC patients compared to healthy control subjects have demonstrated their role as diagnostic target in both corneal ectatic disorders . | Corneal and conjunctival TLR2 TLR4 are overexpressed in eyes with PMD and KC. Both TLR2 TLR4 constitute important diagnostic biomarkers for eyes with PMD KC. The TLR2 TLR4 overexpression is correlated with the disease severity. TLR2 TLR4 overexpression in PMD KC were maintained in the follow up review. |
S001448352030470X | Cellular therapy with mesenchymal stem cells is emerging as an effective option to treat optic neuropathies . In models of retinal degeneration MSC injected in the vitreous body protects injured retinal ganglion cells and stimulate their regeneration however the mechanism is still unknown . Considering the immunomodulating proprieties of MSC and the controversial role of microglial contribution on retinal regeneration we developed an We used whole adult rat retinal explants in co culture with human Wharton s jelly mesenchymal stem cells separated by a transwell membrane and analyzed hMSC effect on both retinal ganglion cells and retinal microglia . hMSC in co culture protected RGCs after 3 days Using a co culture model we demonstrated the paracrine effect of hMSC on RGC survival after injury concomitant with a reduction of microglial population . Paracrine signaling of hMSC also changed microglia phenotype and the expression of antiinflammatory factors in the retina . Our results are consistent with a detrimental effect of microglia on RGC survival and regeneration after injury . | MSC protect retinal ganglion cells by paracrine signaling. Microglial degeneration is potentiated by MSC. Paracrine signaling by MSC shifts microglia to an anti inflammatory phenotype. |
S0014483520304711 | Three dimensional in vitro models are excellent tools for studying complex biological systems because of their physiological similarity to in vivo studies cost effectiveness and decreased reliance on animals . The influence of tissue microenvironment on the cells cell cell interaction and the cell matrix interactions can be elucidated in 3D models which are difficult to mimic in 2D cultures . In order to develop a 3D model the required cell types are derived from the tissues or stem cells . A 3D tissue organ model typically includes all the relevant cell types and the microenvironment corresponding to that tissue organ . For instance a full corneal 3D model is expected to have epithelial stromal endothelial and nerve cells along with the extracellular matrix and membrane components associated with the cells . Although it is challenging to develop a corneal 3D model several attempts have been made and various technologies established which closely mimic the in vivo environment . In this review three major technologies are highlighted organotypic cultures organoids and 3D bioprinting . Also several combinations of organotypic cultures such as the epithelium and stroma or endothelium and neural cultures are discussed along with the disease relevance and potential applications of these models . In the future new biomaterials will likely promote better cell cell and cell matrix interactions in organotypic corneal cultures . | Three dimensional 3D in vitro models are excellent tools for studying complex biological systems. 3D organ models typically include relevant cell types and the microenvironment corresponding to that organ. Organotypic cultures organoids and 3D bioprinting are three major technologies commonly used for 3D in vitro models. |
S0014483520304723 | Degenerative ocular disorders like age related macular degeneration are associated with long term pro inflammatory signals on retinal pigment epithelial cells . In this study we investigated the effect of long term treatment of RPE cells with agonists of toll like receptor 3 TLR 4 and the pro inflammatory cytokine TNF . All tests were conducted with primary porcine RPE . Cells were stimulated with Poly I C LPS or TNF for 1 day 7 days or 4 weeks . Cell viability tests were additionally tested in ARPE 19cells . Cytokine secretion was tested in ELISA phagocytosis in a microscopic assay and expression of RPE65 in Western blot . Barrier function was tested in transwell cultured cells by measuring transepithelial resistance for up to 3 days . LPS and TNF significantly reduce cell viability after 1 day and 7 days Poly I C after 7 days and 4 weeks . LPS Poly I C and TNF significantly induce the secretion of IL 6 and IL 8 at all tested time points . IL 1 is increased by LPS and Poly I C after 1 day but not by TNF . TNF secretion is increased by Poly I C and LPS after 1 day but not at later time points . TGF secretion is not influenced by any stimulus . Concerning RPE function LPS decreased phagocytosis after 7 days while Poly I C and TNF showed no effect . RPE65 expression was strongly reduced by TNF and LPS after 4 weeks . Wound healing capacity was reduced by Poly I C but induced by LPS after 7d and 4 w. Barrier function was not affected by Poly I C or LPS while TNF reduced barrier function after 1h 4h and 3 days . Long term pro inflammatory stimuli reduce RPE viability barrier properties and cellular function and induce pro inflammatory cytokines and therefore may contribute directly to atrophic changes in AMD . | Long term activation of TLR 3 may reduce RPE viability. Long term pro inflammatory stimulation favors IL 8 and IL 6 secretion over IL 1 and TNF. TNF impedes RPE barrier function. Long term stimulation with LPS or TNF reduces RPE65 expression in primary RPE. |
S0014483520304759 | In the adult retina ramifying microglia interact with the outer plexiform layer monitoring the synaptic integrity between photoreceptors and post synaptic target cells . Microglia are reactive during photoreceptor diseases but their disease related function are not fully understood . Retinal explant cultures are model systems used to study degenerative events including photoreceptor degeneration and gliosis . Our culture paradigm with adult porcine retinas subjected to coculture with human A retinal pigment epithelia 19 cells is an experimental approach resulting in improved photoreceptor survival and reduced gliosis . Under the | Microglial cells are reactive in cultured porcine retina. Reactive Iba1 and CD11b immunolabeled microglia localize close to PSD95 immunolabeled photoreceptor terminals in the OPL. Coculture with ARPE cells increase the density of reactive microglia at the OPL. Microglia with dark cytoplasm localized at the OPL can be identified by electron microscopy. The presumptive dark microglia are closely associated with synaptic profiles in the OPL. |
S0014483520304760 | This review details the current understanding of the mechanism of action and corneal effects of mitomycin C for prophylactic prevention of stromal fibrosis after photorefractive keratectomy and includes discussion of available information on dosage and exposure time recommended for MMC during PRK . MMC is an alkylating agent with DNA crosslinking activity that inhibits DNA replication and cellular proliferation . It acts as a pro drug and requires reduction in the tissue to be converted to an active agent capable of DNA alkylation . Although MMC augments the early keratocyte apoptosis wave in the anterior corneal stroma its most important effect responsible for inhibition of fibrosis in surface ablation procedures such as PRK is via the inhibition of mitosis of myofibroblast precursor cells during the first few weeks after PRK . MMC use is especially useful when treating eyes with higher levels of myopia which have shown higher risk of developing fibrosis . Studies have supported the use of MMC at a concentration of 0.02 rather than lower doses for optimal reduction of fibrosis after PRK . Exposure times for 0.02 MMC longer than 40s may be beneficial for moderate to high myopia but shorter exposures times appear to be equally effective for lower levels of myopia . Although MMC treatment may also be beneficial in preventing fibrosis after PRK treatments for hyperopia and astigmatism more studies are needed . Thus despite the clinical use of MMC after PRK for nearly twenty yearswith limited evidence of harmful effects in the corneamany decades of experience will be needed to exclude late long term effects that could be noted after MMC treatment . | Mitomycin C MMC is an alkylating agent with DNA crosslinking activity. MMC inhibits DNA replication and cellular proliferation. MMC inhibits the development of mature myofibroblasts that cause stromal scarring fibrosis. MMC has been found to produce little if any corneal toxicity when used as adjuvant treatment in PRK. |
S0014483520304772 | Oxidative damage in retinal pigment epithelial cells is considered to be a crucial pathogenesis of age related macular degeneration . Although dysregulation of the DNA repair system has been found in RPE cells of AMD patients the detailed molecular mechanisms of this dysregulation and their relationship with the intraocular microenvironment of AMD patients remain unclear . Here we established an RPE model of H | High deacetylation of E2F1 depends on Sirt1 in oxidative stress adapted RPE cells. Deacetylated E2F1 promotes the pentose phosphate pathway through activating the E2F1 HMGA1 G6PD axis. IL 6 induces the phosphorylation of Sirt1 and inhibits its deacetylase activity by activating PI3K AKT mTOR signaling. IL 6 induced acetylation of E2F1 impairs the antioxidant capacity of RPE cells. |
S0014483520304796 | The causes of vitreous humor liquefaction remain unclear . Diabetes accelerates this process and other ocular diseases . The weakening of the blood retina barrier observed with diabetes could enhance the rate of transfer of relatively small molecules such as glucose and phospholipids from the retina to the VH . Glucose and PLs have been detected previously in VH but their regional distributions are not known . The mapping of Glu and PLs in VHs from subjects with and without diabetes could reveal the roles of these molecules in VH liquefaction . Diabetic and non diabetic human eyes were acquired from the Kentucky Lions Eye Bank and frozen immediately . Each VH was removed and halved along the sagittal plane . One half was stamped on a matrix assisted laser desorption ionization plate . Either | The levels of glucose and phospholipids were significantly higher in vitreous humor from diabetics compared to non diabetics. The migration of phospholipids from the lens into the vitreous humor is significant lower relative to that from the retina. Wepropose that the higher abundance species in the posterior VH causes the breakage of the strong H bonding network. |
S0014483520304802 | We are reporting for the first time the synthesis and application of an innovative nanometric system for the controlled topic release of melatonin in the retina . The ethylcellulose nanocapsules were characterized by diverse physicochemical techniques and an in vitro release study was done . A complete ex vivo and in vivo trans corneal permeation and an irritation study were carried out with the new formulations in albino rabbits to which a retinal degenerative model was induced . The results obtained demonstrate that the in vitro release of melatonin transported by nanocapsules is slower when compared to a solution of melatonin . Greater penetration of melatonin through the cornea was demonstrated by ex vivo and in vivo tests . This can be attributable to an enhanced neuroprotective effect of melatonin on retinal ganglion cells when it is included in ethylcellulose nanocapsules compared to a solution of melatonin . These outstanding findings add promising new perspectives to current knowledge about administrations using nano technological tools in the treatment of neurodegenerative diseases at the ocular level . | Eye neuroprotective effect of melatonin loaded polymeric nanocapsules. New drug delivery of melatonin through topical application. Efficient neuroprotection in a retinal degeneration model. Show efficient permeation and low irritation in an eye regeneration model. |
S0014483520304814 | Retinal signaling under dark adapted conditions is perturbed during early diabetes . Additionally dopamine the main neuromodulator of retinal light adaptation is diminished in diabetic retinas . However it is not known if this dopamine deficiency changes how the retina responds to increased light or dopamine . Here we determine whether light adaptation is impaired in the diabetic retina and investigate potential mechanism of impairment . Diabetes was induced in C57BL 6J male mice via 3 intraperitoneal injections of streptozotocin and confirmed by blood glucose levels more than 200mg dL . After 6 weeks whole cell recordings of light evoked and spontaneous inhibitory postsynaptic currents or excitatory postsynaptic currents were made from rod bipolar cells and ON sustained ganglion cells respectively . Light responses were recorded before and after D1 receptor activation or light adaptation background of 950 photonsm | Early diabetes causes retinal deficits in neuronal signaling. These deficits include decreased bipolar cell inhibition and dopamine release. Diabetes deficits increase dark and light adapted retinal ganglion cell excitation. Neuronal signaling changes are not a result of loss of neurons. These changes could lead to overexcitation and damage of retinal ganglion cells. |
S0014483520304838 | The aim of this study was to elucidate the intracellular sources of oxidant species the antioxidant response as well as the main signaling pathways involved in the regulation of the redox balance in the primary visual cortex of rats subjected to an experimental glaucoma model . | The primary visual cortex is target of oxidative damage and both lipids and proteins are vulnerable. NOX4 is a source of ROS in glaucoma contributing to the pro oxidant environment. Glaucoma alters brain GSH GSSG ratio by impairment of GSH synthesis and recycling. iNOS is a source of NO in glaucoma due to NF kB translocation into the nucleus. Nrf2 expression is decreased in glaucoma compromising the cell antioxidant capacity. |
S001448352030484X | In chicks the diurnal patterns of retinal dopamine synthesis and release are associated with refractive development . To assess the within day patterns of dopamine release we assayed vitreal levels of DOPAC using high performance liquid chromatography with electrochemical detection at 4 h intervals over 24h in eyes with experimental manipulations that change ocular growth rates . Chicks were reared under a 12h light 12h dark cycle experiments began at 12 days of age . Output was assessed by modelling using the robust variance structure of Generalized Estimating Equations . | DOPAC is initially reduced under all visual conditions that alter growth rate. The diurnal rhythm in DOPAC is retained under conditions altering eye growth. DOPAC is reduced during the day and the night under visual conditions altering eye growth. |
S0014483520304851 | Elevated intraocular levels of angiogenic cytokines such as vascular endothelial growth factor have been implicated the development of diabetic retinopathy . Over a decade of clinical evidence shows intravitreal injection of anti VEGF agents is associated with decreased disease progression and preservation of vision . However the treatment burden associated with monthly injections limits the effectiveness of existing anti VEGF therapies . Current research has focused on sustained treatment paradigms such as longer acting drugs drug delivery implants and gene therapy . In this study we tested a novel approach by dialyzing proteins from the vitreous using bioceramic implant composed of hydroxyapatite . Preliminary in vitro and in vivo studies demonstrate a high affinity and capacity for VEGF absorption . After three months implantation in New Zealand White Cross rabbits the hydroxyapatite demonstrated good biocompatibility with no inflammation and normal retinal physiology and histology . These studies demonstrate that prolonged VEGF suppression intraocularly may be accomplished with a bioceramic implant . | Vascular Endothelial Growth Factor VEGF plays a crucial role in retinal disease. Anti VEGF drugs are the mainstay of treatment for retinal vascular disease. The short half life of drugs in the eye requires frequent dosing. A solid porous substrate of hydroxyapatite HAp has a strong binding affinity for VEGF. Hydroxyapatite is biocompatible intraocularly. |
S0014483520304863 | In vivo corneal keratocytes reside within a complex 3D extracellular matrix consisting of highly aligned collagen lamellae growth factors and other extracellular matrix components and are subjected to various mechanical stimuli during developmental morphogenesis fluctuations in intraocular pressure and wound healing . The process by which keratocytes convert changes in mechanical stimuli into biochemical signaling is known as mechanotransduction . Activation of the various mechanotransductive pathways can produce changes in cell migration proliferation and differentiation . Here we review how corneal keratocytes respond to and integrate different biochemical and biophysical factors . We first highlight how growth factors and other cytokines regulate the activity of Rho GTPases cytoskeletal remodeling and ultimately the mechanical phenotype of keratocytes . We then discuss how changes in the mechanical properties of the ECM have been shown to regulate keratocyte behavior in sophisticated 2D and 3D experimental models of the corneal microenvironment . Finally we discuss how ECM topography and protein composition can modulate cell phenotypes and review the different methods of fabricating in vitro mimics of corneal ECM topography novel approaches for examining topographical effects in vivo and the impact of different ECM glycoproteins and proteoglycans on keratocyte behavior . | This review highlights how ECM structure and mechanics regulate the behavior of corneal keratocytes. Changes in ECM stiffness regulate myofibroblastic transformation of keratocytes in 2D and 3D culture. Topographical cues can modulate the patterning and differentiation of cultured keratocytes. Rho GTPase activity often coordinates the response of keratocytes to different biochemical and biomechanical cues. |
S0014483520304875 | Corneal stromal keratocytes contribute to the maintenance of corneal transparency and shape by synthesizing and degrading extracellular matrix . They are quiescent in the healthy cornea but they become activated in response to insults from the external environment that breach the corneal epithelium with such activation being associated with phenotypic transformation into fibroblasts . Corneal fibroblasts act as sentinel cells to sense various external stimuliincluding damage associated molecular patterns derived from injured cells pathogen associated molecular patterns of infectious microorganisms and inflammatory mediators such as cytokinesunder pathological conditions such as trauma infection and allergy . The expression of various chemokines and adhesion molecules by corneal fibroblasts determines the selective recruitment and activation of inflammatory cells in a manner dependent on the type of insult . In infectious keratitis the interaction of corneal fibroblasts with various components of microbes and with cytokines derived from infiltrated inflammatory cells results in excessive degradation of stromal collagen and consequent corneal ulceration . Corneal fibroblasts distinguish between type 1 and type 2 inflammation through recognition of corresponding cytokines with their activation by type 2 cytokines contributing to the pathogenesis of corneal lesions in severe ocular allergic diseases . Pharmacological targeting of corneal fibroblast function is thus a potential novel therapeutic approach to prevention of excessive corneal stromal inflammation damage and scarring . | Activation of keratocytes by insults induces their transformation into fibroblasts. Corneal fibroblasts act as sentinel cells that sense various external stimuli. They selectively recruit inflammatory cells after injury infection or allergy. They interact with microbes and inflammatory cells during corneal infection. They contribute to the pathogenesis of corneal lesions in ocular allergy. |
S0014483520304887 | One of the major public health issues is the rising prevalence of cataracts a primary reason for preventable blindness . The causes for the development of age related cataracts and accelerated cataractogenesis in diabetes are multifactorial . Hence this study was designed to examine the status and relationship between the three majorly associated molecular events namely oxidative stress non enzymatic glycation and polyol pathway in age related cataracts with and without diabetes . A total of 472 subjects were distributed into four groups non diabetic subjects with clear lens diabetic subjects with clear lens non diabetic subjects with cataract and diabetic subjects with cataract . Cataracts were graded by slit lamp examination according to the Lens Opacities Classification System III . Age at onset of cataract type of opacity anthropometric measurements and sociodemographic characteristics were recorded and clinical profile was examined . Plasma oxidative stress markers were assessed by estimating the lipid peroxidation end product malondialdehyde protein oxidation products protein carbonyls and DNA oxidative damage marker 8 hydroxy 2 deoxyguanosine . Plasma advanced glycation end products index erythrocyte aldose reductase activity and sorbitol levels were evaluated . After adjusting for age plasma malondialdehyde levels were significantly higher in diabetic cataracts | Nuclear cataract was more predominant in both diabetic and non diabetic subjects. Lipid peroxidation in age related cataracts is independent of diabetes. Only the presence of diabetes augmented plasma advanced glycation index. Disease free aging and controlled diabetes activated the polyol pathway equally. |
S0014483520304899 | The cornea is a highly specialized transparent tissue located at the anterior most surface of the eye . It consists of three main layers the outer stratified squamous epithelium the inner endothelium and the intermediate stroma . Formation of these layers during development involves a complex interaction between ectodermal derived structures such as the overlying head ectoderm with the periocular mesenchyme the latter of which is comprised of neural crest cells and mesoderm derived progenitor cells . Regulation of corneal epithelial development including both epithelial cell fate and stratification has been shown to depend on numerous bi directional mesenchymal epithelial signaling pathways . In this review we pay particular attention to the genes and signaling pathways that involve the POM . | Corneal development depends on bi directional signaling between the overlying head ectoderm and the periocular mesenchyme POM . The POM is comprised of neural crest cells NCC and mesoderm derived progenitor cells. Regulation of corneal epithelial cell fate and stratification has been shown to depend on numerous bi directional mesenchymal epithelial signaling pathways. Key signaling pathways involved in corneal development include Wnt catenin Retinoic Acid TGF and FGF. Key transcription factors controlling corneal development include Pitx2 Foxc1 Pax6 and AP 2. |
S0014483520304905 | NADPH oxidases are activated in ischemic conditions leading to increases in reactive oxygen species and neurotoxicity . The aim of the present study was to investigate the role of NOX in the development of retinal pathologies associated with excitotoxicity and the evaluation of NOX inhibitors as putative therapeutic agents . Sprague Dawley rats were used for the induction of the | NADPH oxidases NOX mediate AMPA induced toxicity. NOX1 inhibition reduces AMPA induced macro microglial activation and cell death. NOX4 inhibition reverses AMPA induced oxidative damage macro microglial activation. NOX as therapeutic targets of retinal neurodegeneration and neuroinflammation. |
S0014483520304917 | Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia . However pharmacological investigations of dopamine in animal models rely heavily on intravitreal or systemic administration which have several limitations for longer term experiments . We therefore investigated whether administration of dopamine as a topical eye drop can inhibit the development of form deprivation myopia in chicks . We also examined whether chemical modification of dopamine through deuterium substitution which might enhance stability and bioavailability can increase dopamine s effectiveness against FDM when given topically . Dopamine or deuterated dopamine Dopamine 1 1 2 2 d Both intravitreal ED Both intravitreal and topical application of dopamine inhibit the development of FDM in a dose dependent manner indicating that topical administration may be an effective avenue for longer term dopamine experiments . Deuterium substitution does not alter the protection afforded by dopamine against FDM when given as either an intravitreal injection or topical eye drop . | Dopamine eye drops inhibit deprivation myopia in a dose dependent manner in chicks. Drops avoid the risks associated with intravitreal injections in chronic treatment. When dose adjusted eye drops were 312 as effective as intravitreal injections. Dopamine similarly inhibits deprivation myopia when chemically modified deuterated . |
S001448352030498X | Aerobic exercise has been shown to play a crucial role in preventing neurological diseases and improving cognitive function . In the present study we investigated the effect of treadmill training on retinal ganglion cells following optic nerve transection in adult rats . We exercised the rats on a treadmill for 5d week or placed control rats on static treadmills . After 3 weeks of exercise the left optic nerve of each rat was transected . After the surgery the rat was exercised for another week . The percentages of surviving RGCs in the axotomized eyes of inactive rats were 67 and 39 at 5 and 7 days postaxotomy respectively . However exercised rats had significant more RGCs at 5 and 7 days after axotomy . Moreover retinal brain derived neurotrophic factor protein levels were significantly upregulated in response to exercise compared with those in the axotomized eyes of inactive rats . Blocking BNDF signaling during exercise by intraperitoneal injections of ANA 12 a BDNF tropomyosin receptor kinase receptor antagonist reduced the number of RGCs in exercised rats to the level of RGCs in the inactive rats effectively abolishing the protection of RGCs afforded by exercise . The results suggest that treadmill training effectively rescues RGCs from neurodegeneration following optic nerve transection by upregulating the expression of BDNF . | Treadmill exercise increases ganglion cell GC survival at 7 days postaxotomy. Treadmill exercise increases BDNF levels in axotomized eyes. Blocking BNDF signaling abolishes the protection of GCs afforded by exercise. Exercise can rescue GCs in axotomized eyes by upregulating BDNF expression. |
S0014483520304991 | The cannabinoid signaling system regulates intraocular pressure in the mouse via a complex system that includes three receptors CB1 GPR18 and GPR119 . In each case activating the receptor lowers IOP but CB1 receptors are found both at sites of aqueous humor inflow and outflow . As such knockout mice for any of these receptors would be expected to have higher than average or at least unchanged intraocular pressure . The current study investigates the unexpected observation that CB1 knockout mice have lower pressure than wild type counterparts by testing various regulators of cannabinoid signaling in murine models of IOP . We now report that a CB1 antagonist has differential effects on IOP SR141716 raises IOP in standard light cycle but lowers IOP in reverse light cycle . This is mimicked by ABD1085 a negative allosteric modulator of CB1 . CB1 inhibitors lower IOP in both normotensive and hypertensive mouse eyes . The pressure lowering effect is absent in CB1 knockout mice . IOP rebounds after the end of treatment but shows no sign of desensitization with daily treatment for a week . Unlike the positive cannabinoid effect antagonist effects are not sex dependent . We propose that there are two mechanisms of action for CB1 one that lowers IOP upon activation and a second with inverse sign that lowers IOP when CB1 is antagonized . The relatively lower pressure in CB1 knockout mouse eyes suggests that this second negative regulation of IOP is dominant . | Cannabinoid CB1 receptor activation and antagonism can each lower ocular pressure. CB1 antagonism appears to be dominant in terms of its effects on ocular pressure. Both CB1 antagonists and negative allosteric modulators can lower ocular pressure. Unlike CB1 agonist effects CB1 antagonist action is not sex dependent. |
S0014483520305005 | The photopic negative response of the electroretinogram reflects retinal ganglion cell function and consequently aids diagnosis of optic nerve diseases including glaucoma . In this study we assessed the efficacy of stimulation parameters for electroretinographic recordings of the multifocal photopic negative response for the detection of glaucoma and compared the diagnostic accuracy of electrophysiological structural and functional measures of glaucoma . We compared the diagnostic performance of the mfPhNR for 6 different stimulation rates in a cohort of 24 controls 10 glaucoma suspects GLA | Multifocal photopic negative response mfPhNR reflects retinal dysfunction. Fast mfPhNR protocols outperform slower protocols in the glaucoma detection. MfPhNR recordings might serve as surrogate marker of ganglion cell damage. |
S0014483520305017 | The cornea is a highly innervated tissue exhibiting a complex nerve architecture distribution and structural organization . Significant contributions over the years have allowed us to come to the current understanding about the corneal nerves . Mechanical or chemical trauma infections surgical wounds ocular or systemic comorbidities can induce corneal neuroplastic changes . Consequently a cascade of events involving the corneal wound healing trophic functions neural circuits and the lacrimal products may interfere in the corneal homeostasis . Nerve physiology drew the attention of investigators due to the popularization of modern laser refractive surgery and the perception of the destructive potential of the excimer laser to the corneal nerve population . Nerve fiber loss can lead to symptoms that may impact the patient s quality of life and impair the best corrected vision leading to patient and physician dissatisfaction . Therefore there is a need to better understand preoperative signs of corneal nerve dysfunction the postoperative mechanisms of nerve degeneration and recovery aiming to achieve the most efficient way of treating nerve disorders related to diseases and refractive surgery . | Corneal nerve impairment after disorders or secondary to refractive surgery can lead to nerve dysfunction. There is not necessarily a correspondence between signs and symptoms of corneal nerve injury. The neural remodeling following refractive surgery is complex and can differ according to the laser technique. |
S0014483520305029 | High intraocular pressure is the most common risk factor associated with glaucoma in humans . While lowering IOP is effective at reducing the rate of retinal ganglion cell loss to date no treatment exists to directly preserve these cells affected by damage to the optic nerve . Recently histone deacetylase 3 has become a potential therapeutic target because it plays an important role in the early nuclear atrophic events that precede RGC death . Conditional knockout or inhibition of HDAC3 prevents histone deacetylation heterochromatin formation apoptosis and eventual RGC loss following acute optic nerve injury . Using these approaches to repress HDAC3 activity we tested whether targeting HDAC3 protects RGCs from ganglion cell specific BRN3A expression loss total somatic cell loss and optic nerve degeneration in the DBA 2J mouse model of spontaneous glaucoma . Targeted ablation of | Conditional knockout of. does not protect against RGC death or axon degeneration in the DBA 2J mouse glaucoma model. Selective inhibition of HDAC3 activity confers mild protection against RGC loss in the DBA 2J mouse model of glaucoma. |
S0014483520305078 | It is reported that Ischemia and reperfusion damage can lead to retinal ganglion cell death and neurodegeneration which in turn can lead to irreversible vision loss . In this study we sought to understand the neuroprotective effect of resveratrol the important activator of sirtuin1 on RGC survival in I R damage model and the molecular mechanism that mediate this effect . Our results show that resveratrol could reverse axonal swelling holes and the chaos of the nucleus in axons of RGCs caused by I R. At the same time resveratrol could also reverse the activation of retinal astrocytes and the loss of RGCs caused by I R. Resveratrol increased the expression of SIRT1 while decreasing the phosphorylation of N terminal kinase . SP600125 decreased the phosphorylation of JNK while increasing the expression of SIRT1 indicating that SIRT1 and JNK can interact with each other . Simultaneous administration of resveratrol and sirtinol neither increased the expression of SIRT1 nor decreased the phosphorylation of JNK indicating that resveratrol affects the phosphorylation of JNK by SIRT1 . In total our research shows that resveratrol treatment significantly reduces apoptosis and axonal degeneration of RGCs and this protection is partly mediated through the SIRT1 JNK pathway . | Retinal I R injury causes damage to both RGCs and their axons. SIRT1 and JNK protein can interact with each other. Resveratrol protected rat RGC axons damage by inhibiting phosphorylation of JNK proteins through SIRT1. |
S001448352030508X | The meninges not only surround the brain and the spinal cord but also the optic nerve . Meningeal derived extracellular matrix is a crucial component of the pial basement membrane glia limitans and important for maintenance of optic nerve axon integrity homeostasis and retinal ganglion cell health . To get closer insight into optic nerve meningeal derived ECM composition we performed proteomic analysis of the sheep optic nerve subarachnoid space . Candidate components were confirmed in cultures of primary human meningothelial cells and human optic nerve samples . Sheep optic nerve SAS samples were analysed by LC MS identified proteins were matched to their human orthologs and filtered using gene lists representing all major ECM components . To validate these findings digital droplet PCR to evaluate mRNA expression of all candidate components identified was performed on cultures of phMECs . In addition one protein per major ECM group was stained on human optic nerve sections and on phMEC cultures . Employing LC MS 1273 proteins were identified and subjected to bioinformatic analysis . Gene ontology analysis revealed six out of forty four collagen types three out of eleven laminin subunits and six out of twenty seven hyaluronan binding proteins C1q binding protein neurocan brevican and hyalaluronan proteoglycan link protein 2 were present in our cohort . DdPCR in phMEC cell culture confirmed presence of all candidate components except NCAN BCAN and HAPLN2 . Immunohistochemistry staining on human optic nerve sections and immunofluorescence staining on in vitro cultured phMECs showed strong immunopositivity for collagen typeI 1 laminin1 and VCAN . Fibronectin was exclusively present in cultures of phMECs . Using a combined bioinformatics and immunohistological approach we describe the ECM composition of the optic nerve subarachnoid space . As this space plays an important role in maintaining optic nerve function a better understanding of ECM composition in this delicate environment might be key to further pathophysiological insight into optic nerve degeneration and associated disorders . | 1273 proteins found in sheep optic nerve subarachnoid space pia arachnoid dura . 1143 matches between sheep and human proteins using bioinformatic analysis. Major proteins found included collagens laminins and hyaluronan binding proteins. Verification in meningothelial cell culture and human optic nerve samples performed. |
S0014483520305091 | Long noncoding RNA potassium voltage gated channel subfamily Q member 1 opposite strand antisense transcript 1 takes part in diabetic cataract progression . This research aims to analyze the function and mechanism of KCNQ1OT1 on viability migration and epithelial mesenchymal transition in lens epithelial cells . 20 diabetic cataract posterior lens capsule tissues and normal samples were collected . Lens epithelial cells were stimulated via high glucose . The levels of KCNQ1OT1 miR 26a 5p integrin V TGF Smad3 and phosphorylated Smad3 were measured via quantitative real time polymerase chain reaction or Western blot . Cell viability migration and EMT were analyzed via MTT wound healing transwell and Western blot assays . The target relationship between miR 26a 5p and KCNQ1OT1 or ITGAV was determined via luciferase reporter assay . KCNQ1OT1 was up regulated and miR 26a 5p level was reduced in diabetic cataract tissues and HG treated SRA01 04 cells . Silence of KCNQ1OT1 or miR 26a 5p up regulation repressed cell viability migration and EMT in SRA01 04 cells stimulated via HG . KCNQ1OT1 could target miR 26a 5p and controlled cell viability migration and EMT via regulating miR 26a 5p . ITGAV was targeted via miR 26a 5p and positively regulated via KCNQ1OT1 . ITGAV overexpression promoted cell viability migration and EMT in HG treated SRA01 04 cells which were mitigated by KCNQ1OT1 silence . KCNQ1OT1 knockdown mitigated HG induced the activation of TGF Smad3 signaling by regulating miR 26a 5p . KCNQ1OT1 knockdown represses cell viability migration and EMT through miR 26a 5p ITGAV TGF Smad3 axis in SRA01 04 cells under HG condition providing a new target for the treatment of diabetic cataract . | KCNQ1OT1 expression was increased in diabetic cataract tissues and high glucose treated SRA01 04 cells. KCNQ1OT1 regulated cell viability migration and epithelial mesenchymal transition by targeting miR 26a 5p. ITGAV promoted cell viability migration and epithelial mesenchymal transition in high glucose treated SRA01 04 cells. |
S0014483520305108 | Choroidal all trans retinoic acid may play a key role in the control of postnatal eye growth in a variety of vertebrates through modulation of scleral extracellular matrix synthesis and may therefore play a crucial role in the development of myopia . In the chick eye choroidal atRA synthesis is exclusively regulated by its synthesizing enzyme retinaldehyde dehydrogenase 2 . In chicks and humans RALDH2 has been detected in a population of hitherto uncharacterized choroidal cells.Therefore the aim of this study was to identify the RALDH2 cell type in the choroid and determine how these cells modulate atRA concentrations during periods of visually guided eye growth . Chicks wore translucent goggles on one eye for 10 days and choroids were analyzed for RALDH activity and RALDH2 protein expression at days 0 1 4 7 15 following removal of the goggle choroids from contralateral eyes served as controls . The presence of RALDH2 cells was assessed in chick choroid wholemounts using multiphoton microscopy . RALDH2 protein expression was measured by western blot and RALDH2 activity was assessed via HPLC quantification of atRA . Cell proliferation was assessed by BrdU labelling in combination with RALDH2 immunohistochemistry . For characterization of RALDH2 cells immunohistochemistry for various tissue specific markers was applied in chicken and human donor tissue followed by confocal microscopy . In the chick and human choroid RALDH2 cells with variable morphology were present in the stroma and adjacent to choroidal blood vessels . In chick wholemounts RALDH2 cells were concentrated toward the choriocapillaris and their number increased nearly linearly between 1 and 7 days of recovery and plateaued between 7 and 15 days compared to corresponding controls . A significant increase in choroidal RALDH2 protein concentration and atRA synthetic activity was observed by four days of recovery by western blot and HPLC respectively . A 3 fold increase in RALDH2 BrDU cells was observed following 4 days of recovery compared to controls . In chick choroids the vast majority of RALDH2 cells co expressed Col1 propetide but did not co label with any other antibodies tested . In human choroid some but not all RALDH2 cells colocalized with vimentin but were negative for all other antibodies tested . RALDH2 cells represent a novel cell type in the chick and human choroid . Our findings that some human RALDH2 cells were positive for vimentin and all chick RALDH2 cells were positive for Col1 suggest that RALDH2 cells most closely resemble perivascular and stromal fibroblasts . The increased number of RALDH2 BRDU cells following 4 days of recovery suggests that choroidal atRA concentrations are partially controlled by proliferation of RALDH2 cells . The identification of this choroidal cell type will provide a broader understanding of the cellular events responsible for the regulation of postnatal ocular growth and may provide new avenues for specifically targeted strategies for the treatment of myopia . | Choroidal retinoic acid synthesis plays a role in postnatal ocular growth control. Retinoic acid synthesis is regulated by retinaldehyde dehydrogenase 2. Retinaldehyde dehydrogenase 2 is expressed by a novel choroidal cell type. Proliferation of this novel cell type regulates choroidal retinoic acid synthesis. |
S001448352030511X | The aim of this study is to analyze the concentrations of cytokines in tear of hospitalized COVID 19 patients compared to healthy controls . Tear samples were obtained from 41 healthy controls and 62 COVID 19 patients . Twenty seven cytokines were assessed interleukin 1b IL 1RA IL 2 IL 4 IL 5 IL 6 IL 7 IL 8 IL9 IL 10 IL 12 IL 13 IL 15 IL 17 eotaxin fibroblast growth factor basic granulocyte colony stimulating factor granulocyte monocyte colony stimulating factor interferon interferon gamma induced protein monocyte chemo attractant protein 1 macrophage inflammatory protein 1a MIP 1b platelet derived growth factor regulated on activation normal T cell expressed and secreted tumor necrosis factor and vascular endothelial growth factor .In tear samples of COVID 19 patients an increase in IL 9 IL 15 G CSF GM CSF IFN PDGF and VEGF was observed along with a decrease in eotaxin compared to the control group . A poor correlation between IL 6 levels in tear and blood was found . IL 1RA and GM CSF were significantly lower in severe patients and those who needed treatment targeting the immune system . Tear cytokine levels corroborate the inflammatory nature of SARS CoV 2 . | Hyperinduction of proinflammatory cytokine plays an important role in the disease progression of patients infected with SARS CoV 2. Tear levels of cytokines are increased in COVID 19 patients. |
S0014483520305121 | Ongoing research using cell transplantation and viral mediated gene therapy has been making progress to restore vision by retinal repair but targeted delivery and complete cellular integration remain challenging . An alternative approach is to induce endogenous Mller glia to regenerate lost neurons and photoreceptors as occurs spontaneously in teleost fish and amphibians . Extracellular vesicles can transfer protein and RNA cargo between cells serving as a novel means of cell cell communication . We conducted an | Intravitreal injection of extracellular vesicles can induce proliferation. In vivo screen identified 12 sources of extracellular vesicles capable of inducing proliferation. Extracellular vesicles from C6 cells promote Mller glia derived proliferation. Extracellular vesicles from C6 cells induce Ascl1a expression. |
S0014483520305133 | Reactive oxygen species normally play an important physiological role in health regulating cellular processes and signal transduction . The amount of ROS is usually kept in fine balance with the generation of ROS largely being offset by the body s antioxidants . A tipping of this balance has increasingly been recognised as a contributor to human disease . The retina as a result of its cellular anatomy and physical location is a potent generator of ROS that has been linked to several major retinal diseases . This review will provide a summary of the role of oxidative stress in the pathogenesis of diabetic retinopathy age related macular degeneration myopia retinal vein occlusion retinitis pigmentosa and retinopathy of prematurity . Therapies aimed at controlling oxidative stress in these diseases are also examined . | Reactive oxygen species play a major role in the pathogenesis of a variety of retinal diseases. This review summarises our current understanding of oxidative stress and its effect on a variety of retinal diseases. Minimising oxidative stress can prove to be crucial in preventing disease occurrence or progression. |
S0014483520305145 | Bio engineering technologies are currently used to produce biomimetic artificial corneas that should present structural chemical optical and biomechanical properties close to the native tissue . These properties are mainly supported by the corneal stroma which accounts for 90 of corneal thickness and is mainly made of collagen type I . The stromal collagen fibrils are arranged in lamellae that have a plywood like organization . The fibril diameter is between 25 and 35nm and the interfibrillar space about 57nm . The number of lamellae in the central stroma is estimated to be 300 . In the anterior part their size is 1040m . They appear to be larger in the posterior part of the stroma with a size of 60120m . Their thicknesses also vary from 0.2 to 2.5m . During development the acellular corneal stroma which features a complex pattern of organization serves as a scaffold for mesenchymal cells that invade and further produce the cellular stroma . Several pathways including Bmp4 Wnt catenin Notch retinoic acid and TGF in addition to EFTFs including the mastering gene Pax 6 are involved in corneal development . Besides retinoic acid and TGF seem to have a crucial role in the neural crest cell migration in the stroma . Several technologies can be used to produce artificial stroma . Taking advantage of the liquid crystal properties of acid soluble collagen it is possible to produce transparent stroma like matrices with native like collagen I fibrils and plywood like organization where epithelial cells can adhere and proliferate . Other approaches include the use of recombinant collagen cross linkers vitrification plastically compressed collagen or magnetically aligned collagen providing interesting optical and mechanical properties . These technologies can be classified according to collagen type and origin presence of telopeptides and native like fibrils structure and transparency . Collagen matrices feature transparency 80 for the appropriate 500 m thickness . Non collagenous matrices made of biopolymers including gelatin silk or fish scale have been developed which feature interesting properties but are less biomimetic . These bioengineered matrices still need to be colonized by stromal cells to fully reproduce the native stroma . | During development mesenchymal cells invade the organized acellular corneal stroma and further produce the cellular stroma. Collagen liquid crystal properties permit producing transparent matrices with collagen I fibrils and plywood organization. Other approaches include recombinant collagen cross linkers compressed collagen or magnetically aligned collagen. Bioengineered matrices still need to be colonized by stromal cells to fully reproduce the native stroma. |
S0014483520305157 | Transient potential receptor vanilloid 4 is an ion channel responsible for sensing osmotic and mechanical signals which in turn regulates calcium signaling across cell membranes . TRPV4 is widely expressed throughout the body and plays an important role in normal physiological function as well as different pathologies however its role in the eye is not well known . In the eye TRPV4 is expressed in various tissues such as the retina corneal epithelium ciliary body and the lens . In this review we provide an overview on TRPV4 structure activation mutations and summarize the current knowledge of TRPV4 function and signaling mechanisms in various locations throughout the eye as well as its role in ocular diseases such as glaucoma and diabetic retinopathy . Based on the available data we highlight the therapeutic potential of TRPV4 as well as the shortcomings of current research . Finally we provide future perspectives on the implications of targeting TRPV4 to treat various ocular pathologies . | TRPV4 is expressed in various cells and tissues of the eye. TRPV4 is mechanosensor and regulates ion and water homeostasis in the eye. TRPV4 modulates intraocular pressure and involved in glaucoma. TRPV4 is implicated in ischemia induced neovascularization and diabetic retinopathy. |
S0014483520305169 | The transforming growth factor beta plays an essential role in the pathogenesis of some ophthalmologic diseases including neovascular age related macular degeneration and proliferative vitreoretinopathy . TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor which together activate several genes including VEGFA . TGFB treated ARPE 19cells show an increased proliferation rate and undergo epithelial to mesenchymal transition . Since microRNAs are capable of inhibiting the translation of multiple genes we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels . In this study we focused on two miRNAs miR 302d and miR 93 which inhibit TGFB signalling pathway and therefore TGFB induced EMT transition as well as VEGFA secretion from ARPE 19cells . Furthermore we could show that both miRNAs can retransform TGFB stimulated mesenchymal ARPE 19cells towards the morphological epithelial like state . Taken together transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies . | miR 302d and miR 93 are capable of inhibiting TGFB mediated VEGFA secretion from ARPE 19 cells by directly targeting TGFBR2 as well as VEGFA. Both miRNAs can prevent TGFBinduced EMT of ARPE 19 cells in vitro mainly by inhibiting TGFBR2 at the transcriptional and translational level. Both miRNAs can revert TGFB induced mesenchymal ARPE 19 cells towards an epithelial like state and therefore promote MET. |
S0014483520305236 | The dog is an important animal model for tear dysfunction diseases however to date the electrolyte composition of the dog s tears is unknown . The aim of this study was to analyze the electrolyte content of canine tears and compare it to serum and plasma . Tear samples were collected from 18 eyes of 9 dogs . Blood for serum was collected in tubes with no anticoagulants plasma was obtained by using two different anticoagulants Citrate Phosphate Dextrose and heparin . The electrolytes were measured in all samples analyzed and compared . Most of the electrolyte values in tears were statistically different from electrolyte values in serum and plasma . Potassium and chloride values were significantly higher in tears compared to serum and plasma while calcium and phosphate values were significantly lower . Sodium values in tears were higher than in serum and heparinized plasma but lower than CPD plasma . Bicarbonate values were lower in tears compared to serum and heparinized plasma but was not statistically different than CPD plasma . While magnesium values were lower in tears compared to serum and heparinized plasma the difference was not statistically different . Herein we report for the first time the electrolyte composition of the canine tears and its comparison to serum and plasma . | The dog is an important animal model for tear dysfunction diseases. This is a first report of electrolyte composition in canine tears and its comparison to serum and plasma. Establishing the electrolyte parameters in canine tears may help with further studies of corneal surface disease |
S0014483520305248 | Cannabinoids are part of an endogenous signaling system found throughout the body including the eye . Hepler and Frank showed in the early 1970s that plant cannabinoids can lower intraocular pressure an effect since shown to occur via cannabinoid CB1 and GPR18 receptors . Endocannabinoids are synthesized and metabolized enzymatically . Enzymes implicated in endocannabinoids breakdown include monoacylglycerol lipase and fatty acid amide hydrolase but also ABHD12 NAAA and COX 2 . Inhibition of MAGL activity raises levels of the endocannabinoid 2 arachidonoyl glycerol and substantially lowers IOP . Blocking other cannabinoid metabolizing enzymes or cannabinoid transporters may similarly contribute to lowering IOP and so serve as therapeutic targets for treating glaucoma . We have tested blockers for several cannabinoid metabolizing enzymes and transporters for their ability to alter ocular pressure in a murine model of IOP . Of FAAH ABHD12 NAAA and COX2 only FAAH was seen to play a role in regulation of IOP . Only the FAAH blocker URB597 lowered IOP but in a temporally diurnally and sex specific manner . We also tested two blockers of cannabinoid transport finding that each lowered IOP in a CB1 dependent manner . Though we see a modest limited role for FAAH our results suggest that MAGL is the primary cannabinoid metabolizing enzyme in regulating ocular pressure thus pointing towards a role of 2 arachidonoyl glycerol . Interestingly inhibition of cannabinoid transport mechanisms independent of hydrolysis may prove to be an alternative strategy to lower ocular pressure . | Endocannabinoid metabolizing enzymes and transporters may offer an attractive target to regulate ocular pressure. Blocking either of the hypothesized endocannabinoid transporters lowers ocular pressure. Fatty acid amide hydrolase FAAH appears to play a complex sex and time dependent role in regulating endocannabinoids. COX2 ABHD12 and NAAA do not appear to contribute to endocannabinoid metabolism in the context of regulation of ocular pressure. |
S001448352030525X | Neovascularization is a critical process in the pathophysiology of neovascular eye diseases . Although anti VEGF therapy has achieved remarkable curative effects complications limited efficacy and drug resistance remain the prominent problems . DCZ3301 an aryl guanidino compound was reported to have anti tumor activity in the previous studies . Here we demonstrated the effects of DCZ3301 on human umbilical vein endothelial cell | DCZ3301 retards the proliferation migration and tube formation of HUVECs. DCZ3301 inhibits choroid microvascular sprouting. DCZ3301 diminishes the area of corneal neovascularization after alkali burn in mice. DCZ3301 induces spontaneous apoptosis of HUVECs by suppressing the activation of PI3K AKT and ERK1 2 pathways. |
S0014483520305261 | Glaucoma is still a poorly understood disease with a clear need for new biomarkers to help in diagnosis and potentially offer new therapeutic targets . We aimed to determine if the metabolic profile of aqueous humor as determined by nuclear magnetic resonance spectroscopy allows the distinction between primary open angle glaucoma patients and control subjects and to distinguish between high tension and normal tension glaucoma . We analysed the AH of patients with POAG NTG and control subjects . | Aqueous humor metabolomics achieved AUC 0.93 between glaucoma patients and controls. Aqueous humor shows neural protection and damage happen simultaneously in glaucoma. Nuclear magnetic resonance spectroscopy distinguishes glaucoma patients and controls. |
S0014483520305273 | Antibiotic resistance is increasing even in ocular pathogens therefore the interest towards antiseptics in Ophthalmology is growing . The aim of this study was to analyze the in vitro antimicrobial efficacy and the in vitro effects of an ophthalmic formulation containing hexamidine diisethionate 0.05 polyhexamethylene biguanide 0.0001 disodium edetate 0.01 dexpanthenol 5 and polyvinyl alcohol 1.25 on cultured human corneal and conjunctival cells . The in vitro antimicrobial activity was tested on | Topical antibiotic overuse increases microbial resistance. Therefore the interest towards antiseptics is growing. Keratosept ophthalmic solution showed a good antimicrobial activity in vitro. Keratosept showed low toxicity on corneal and conjunctival epithelial cells. |
S0014483520305285 | Corneal opacities affect vision for millions of individuals worldwide . Fibrotic scar tissues accumulate in reaction to inflammatory responses and remain permanently in corneal stroma and conventionally correctable only by donor corneal transplantation . Numerous studies have explored innovative approaches to reverse corneal scarring through non surgical means however existing mouse models limit these studies due to the lack of visibility of scar tissue in mouse corneas with steep curvature . Here we reported that corneal scarring was modelled using a transgenic mouse line TgDJ124Gsat in which enhanced green fluorescence protein reporter expression was driven by the promoter of collagen 3a1 | Corneal scarring of Tg Col3a1 EGFP DJ124Gsat mice was similar as wildtype mice. EGFP expression was aligned with. upregulation after corneal injuries. EGFP expressing cells and fluorescent intensity were correlated to corneal scarring. Tg COL3a1 EGFP DJ124Gsat mice allow real time assessment of corneal scarring. |
S0014483520305297 | Previous studies have reported that endothelial to mesenchymal transition contributes to pathological fibrosis in proliferative diabetic retinopathy . The hypothesis of our study was that exosomes from high glucose treated ARPE19cells reprogram endothelial cell behavior in HG conditions by transferring their genetic contents . Our study showed that ARPE19 derived exosomes were internalized by human umbilical vein endothelial cells . Additionally miR 202 5p a miRNA known to target TGFR2 was enriched in ARPE19 derived exosomes . A dual luciferase reporter assay qPCR and western blotting were used to characterize the expression of miR 202 5p and phosphorylation of the TGF Smad pathway proteins . We showed that miR 202 5p containing exosomes suppressed HUVEC cell growth migration and tube formation . Furthermore TGFR2 was confirmed as the target of miR 202 5p . A dual luciferase reporter assay showed that TGFR2 expression was negatively regulated by miR 202 5p . We also showed that miR 202 5p containing exosomes suppressed HG induced EndoMT . These collective results suggested that ARPE derived exosomes may serve as significant mediators of cell to cell crosstalk to suppress EndoMT by transferring miR 202 5p through the TGF Smad pathway and may be a potential treatment for PDR patients . | ARPE19 cells release exosomes in high glucose condition. Exosomes from high glucose treated ARPE19 cells modulate phenotypes of HUVECs. Exosomal miR 202 5p regulates the TGF signaling pathway by targeting TGFR2. |
S0014483520305303 | Myofibroblasts are alpha smooth muscle actin cells that have a critical role in the corneal stromal response to infections injuries and surgeries and which produce corneal scarring fibrosis when they develop in excess . These contractile and opaque cellsproduce large amounts of disordered extracellular matrix and develop from keratocyte derived corneal fibroblasts or bone marrow derived fibrocytes and possibly other cell types in response to TGF1 TGF2 and PDGF from the epithelium tears endothelium and other stromal cells . Recent proteomic analyses have revealed that the myofibroblasts that develop from different progenitors aren t interchangeable but have major differences in protein expression and functions . Absence or defective regeneration of the epithelial basement membrane and or Descemet s basement membrane results in development and persistence of myofibroblasts in the corneal stroma . The functions of myofibroblasts in the cornea include production of volume additive ECM tissue contraction production of various growth factors cytokines and chemokines that regulate stromal cells including other myofibroblasts production of collagenases and metalloproteinases involved in tissue remodeling and the expression of toll like receptors that likely have critical roles in the clearance of bacteria and viruses causing corneal infections . | Myofibroblasts are the major contributor to corneal fibrosis after injury or infection. Myofibroblasts are dependent on TGF beta 1 or 2 for development and survival. Corneal myofibroblasts are derived from keratocyte and fibrocyte derived precursors. Myofibroblasts derived from different precursors have differential gene expression. |
S0014483520305327 | The prevalence of nonsense mutations as a class within genetic diseases such as inherited retinal disorders presents an opportunity to develop a singular common therapeutic agent for patients whose treatment options are otherwise limited . We propose a novel approach to addressing IRDs utilizing Eukaryotic Ribosome Selective Glycosides ELX 01 and ELX 06 delivered to the eye by intravitreal injection . We assessed read through activity | ELX 01 and ELX 06 induce read through of the. nonsense mutation. effects translated to. production of melanin in albino mouse eye. Results establish exposure range for developing a sustained release IVT formulation. |
S0014483520305339 | Retina one of the highest oxygen demanding tissues is vulnerable to vascular insufficiencies and various ocular vascular disorders can cause chronic retinal ischemia . To investigate the pathophysiology rodent models developed by bilateral common carotid artery occlusion have been utilized . However mice lack posterior communicating arteries in the circle of Willis and can not endure the brain ischemia induced by the bilateral occlusion . A mouse model to better reflect the localized ischemic stress in the retina without affecting the brain is still needed . Here we established a mouse model of ischemic injury by permanent unilateral common carotid artery occlusion . Adult male mice were subjected to UCCAO and changes in the ipsilateral retina were examined in comparison with the contralateral retina . Delayed perfusion was observed in the ipsilateral retina right after the occlusion and was not recovered later on . Common features of retinal ischemia were observed hypoxia inducible factor stabilization upregulation of hypoxia responsive genes altered levels of cytokines and chemokines . Activation of astrocytes and Mller cells in the inner retina was detected at day 2 and thinning of the inner retinal layer became significant at week 10 . Together our model can simulate retinal ischemia with morphological and molecular changes . It can be utilized to investigate pathophysiology of ischemic retinopathies . | A mouse model for retinal hypoperfusion injury was established. Unilateral common carotid artery occlusion induces ischemia in the ipsilateral retina. Delayed perfusion and upregulation of. were persistent 4 weeks after the occlusion. Inner retinal thinning became remarkable 10 weeks after the occlusion. |
S0014483520305352 | The Lebers hereditary optic neuropathy is a rare disease caused by mitochondrial DNA mutations . Beside primary mutations the effect of secondary mtDNA mutations in still unclear . We examined the effect of secondary mtDNA mutations on secondary structure of different mitochondrial RNAs . Whole mitochondrial genome sequence of LHON patients has been obtained from in six non related pedigrees by Sanger sequencing method . The effect of mutations located in mitochondrial RNA genes was examined by creating in silico models of RNA secondary and regional 3D structure accompanied by sequence conservation analysis . All three primary LHON mutations were revealed in study families . Four mutations in MT RNR1 gene were identified and only an m.1555A G causes significant changes of secondary structure of mitochondrial 12S ribosomal RNA while it is the only mutation which does not alter its 3D structure . Five mutations were discovered in MT RNR2 gene and all of them induced substantial alterations of mitochondrial 16S rRNA secondary structure . Significant changes of mitochondrial 16S rRNA 3D structure are caused by m.1811A G m.2706A G m.3010G A and m.3197T C. A single insertion variant has been found in the MT TP gene which encodes mitochondrial transfer RNA for Proline . This mutation does not cause substantial changes of tRNA for Proline secondary structure while the 3D geometry remains without major changes . Most of the mutation loci exhibited high level of sequence conservation . Presence of multiple mutations in a single family appears to cause more extensive changes in mitochondrial 12S and 16S rRNA then their individual influence . The effect of discovered mutations on in silico modelled RNA structure is in a significant correlation with the present knowledge about the potential of these mutation to participate in the pathophysiology of LHON and other human diseases . The presence of certain multiple mitochondrial RNA mutations could be a possible explanation of LHON clinical presentation in some families . All revealed mutations have been evaluated for the first time in terms of in silico structural modelling . The application of bioinformatics tools such as secondary and 3D RNA structure prediction can have a great advantage in better understanding of the molecular standpoint of the LHON pathophysiology and clinical phenotype . | LHON patients have secondary mutations of mitochondrial RNA genes. Some mutations significantly influence secondary and 3D structure of mitochondrial RNAs. There is a correlation between structural rRNA changes and mutations pathogenicity. Effect of described mutations was modeled for the first time in this study. Clinical management of LHON can benefit from basic research. |
S0014483520305364 | To describe the location and morphometric characteristics of the human limbal lymphatic vasculature and its relation to the marginal corneal vascular arcades . confocal microscopic imaging and immunofluorescence double staining for CD 31 and D2 40 of histological en face sections using 12 preserved human cadaveric corneoscleral discs were performed followed by a semi automated morphometric analysis of the two dimensional vascular network architecture . CM confirmed the presence of 2 distinct vascular networks . The haematic limbal vascular complex extended further into the cornea forming typical MCAs . The lymphatic limbal vascular complex was peripheral from the termination of Bowman s layer and was also found to be peripheral to and deeper than the HLVC . LLVC and HLVC were significantly different with respect to vessel diameter segment length and wall thickness . The lymphatic vasculature of the human corneoscleral limbal region displays specific morphometric features that allow its differentiation from haematic vessels using CM . | Confocal microscopy lacks validation to image the limbal lymphvasculature. Correlating confocal and immunofluorescence microscopy validates lymphatic imaging. We describe en face morphological parameters to reliably identify limbal lymphatic vessels using confocal microscopy. |
S0014483520305376 | We aimed to investigate the associations among lens epithelium telomere length cataract types and systemic pro senescence factors in patients with age related cataract . In this prospective study the general demographic factors body mass index smoking history depression hypertension diabetes various psychological measures and uncorrected distant visual acuity of patients with age related cataract were recorded . Lens Opacities Classification System III scores and lens density measured by Scheimpflug imaging were used to evaluate the cataracts . LETL was measured by real time polymerase chain reaction . Correlations among these parameters were analyzed . The LOCS III nuclear opalescence score was associated with age 0.053 | LOCS III nuclear opacity score but not cortical or posterior subcapsular score was influenced by systemic factors. LOCS III scores were positively associated with maximum lens densities. With lens epithelium telomere length reduction average lens density decreased significantly. Association of lens epithelium telomere length with mean cortical lens density was larger than nucleus. |
S001448352030539X | Glaucoma is characterized by the neurodegeneration of retinal ganglion cells and the optic nerve . Numerous studies have reported that S100A4 participates in the metastasis of tumor cells and nerve protection . This study was intended to explore the role of S100A4 on RGCs under retinal ischemia reperfusion injury in mice . C57BL 6J mice were used to induce retinal I R injury . The intravitreal administration of rAAV EF1 s100a4 EGFP WPRE or rAAV EF1 EGFP WPRE Pa was performed 4 weeks before I R injury . Expression of S100A4 was detected by quantitative real time PCR immunofluorescence staining of retinal sections and western blot . Surviving RGCs were quantified using immunofluorescence staining . Staining of TUNEL was utilized to evaluate the apoptosis of retinal cells . Electroretinogram was used to analyze retinal function . Expression of Akt phospho Akt Bcl 2 and Bax were determined using western blotting to investigate the potential mechanisms of S100A4 . Retinal S100A4 level had no statistical difference 7 days after I R injury . The rAAV S100A4 was clearly demonstrated by the green fluorescence protein in many layers of the retina after intravitreal injection and up regulated the expression of S100A4 . I R injury resulted in an increase of the apoptosis of retinal cells and the reduction of surviving RGCs however overexpressed S100A4 inhibited the apoptosis of cells and a decrease of RGCs . ERG analysis showed a drop on amplitude of a wave and b wave was impeded to some extent by overexpressing of S100A4 . Up regulation of S100A4 raised the expression of phospho Akt and reduced Bax expression . Nevertheless there were no significant changes in the levels of Bcl 2 and total Akt . Our results indicate the neuroprotective effects of overexpressed S100A4 on RGCs by activating the Akt pathway and then inhibiting the apoptosis of cells after I R injury . The use of S100A4 protein may be a novel therapeutic strategy for glaucoma . | The neuroprotective effects of S100A4 on RGCs were reported for the first time. Overexpressed S100A4 inhibited the damage of retinal function induced by retinal ischemia reperfusion injury. The neuroprotection of overexpressed S100A4 achieved by activating Akt signaling and then inhibiting the apoptosis of cells. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.