Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Lycium barbarum polysaccharide inhibits retinal neovascularization and inflammation in vitro and in vivo

AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N2),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

The retinal pigment epithelium:Functions and roles in ocular diseases

The retinal pigment epithelium(RPE)between retinal photoreceptors and choroidal capillaries is a single layer of cells that are of critical importance to the eye.RPE cells are derived from the anterior neural plate of neuroectodermal origin.Instructed by specific molecules and signaling pathways,the RPE undergoes formation and maturation to form a functional unit together with photoreceptors.The RPE plays crucial roles in maintaining normal retinal structure and functions,such as phagocytosis;barrier function;transportation of nutrients,ions,and water;resistance to oxidative damage;maintenance of visual cycle;and production of various important factors.RPE cells have an efficient metabolic machinery to provide sufficient energy to the retina.RPE dysfunction or atrophy can lead to many retinopathies,such as age-related macular degeneration and proliferative vitreoretinopathy.Here,we discuss RPE development,functions,and roles in various ocular diseases,and the mechanisms involved.A better understanding of the functions of the RPE and related regulatory pathways may help identify novel or better therapies for the treatment of many blinding diseases.

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events:a prospective observational study

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations.However,the ability of retinal vasculature changes,specifically focusing on retinal vessel diameter,to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively.While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events,they have not incorporated this information into a predictive model.Therefore,this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke.Additionally,we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors.We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University.All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years.We found that,after adjusting for related risk factors,patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin(MAD_(0.5-1.0DD))of≥74.14μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin(MVD_(0.5-1.0DD))of≥83.91μm tended to experience recurrent cerebrovascular events.We established three multivariate Cox proportional hazard regression models:model 1 included traditional risk factors,model 2 added MAD_(0.5-1.0DD)to model 1,and model 3 added MVD0.5-1.0DD to model 1.Model 3 had the greatest potential to predict subsequent cerebrovascular events,followed by model 2,and finally model 1.These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke,and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Circadian rhythm disruption and retinal dysfunction:a bidirectional link in Alzheimer’s disease?

Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,Alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of Alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

Retinal displacement after surgery for idiopathic macular hole

AIM:To review and summarize the mechanism hypothesis,influencing factors and possible consequences of macular retinal displacement after idiopathic macular hole(IMH)surgery.METHODS:PubMed and Web of Science database was searched for studies published before April 2023 on“Retinal displacement”,“Idiopathic macular holes”,and“Macular displacement”.RESULTS:Recently,more academics have begun to focus on retinal displacement following idiopathic macular holes.They found that internal limiting membrane(ILM)peeling was the main cause of inducing postoperative position shift in the macular region.Moreover,several studies have revealed that the macular hole itself,as well as ILM peeling method,will have an impact on the result.In addition,this phenomenon is related to postoperative changes in macular retinal thickness,cone outer segment tips line recovery,the occurrence of dissociated optic nerve fiber layer(DONFL)and the degree of metamorphopsia.CONCLUSION:As a subclinical phenomenon,the clinical significance of postoperative macular displacement cannot be underestimated as it may affect the recovery of anatomy and function.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

Medical image registration and its application in retinal images:a review

Medical image registration is vital for disease diagnosis and treatment with its ability to merge diverse informa-tion of images,which may be captured under different times,angles,or modalities.Although several surveys have reviewed the development of medical image registration,they have not systematically summarized the existing med-ical image registration methods.To this end,a comprehensive review of these methods is provided from traditional and deep-learning-based perspectives,aiming to help audiences quickly understand the development of medical image registration.In particular,we review recent advances in retinal image registration,which has not attracted much attention.In addition,current challenges in retinal image registration are discussed and insights and prospects for future research provided.

Reliability of the ocular trauma score for the predictability of traumatic and post-traumatic retinal detachment after open globe injury

AIM: To elucidate the question of whether the ocular trauma score(OTS) and the zones of injury could be used as a predictive model of traumatic and post traumatic retinal detachment(RD) in patients with open globe injury(OGI).METHODS: A retrospective observational chart analysis of OGI patients was performed. The collected variables consisted of age, date, gender, time of injury, time until repair, mechanism of injury, zone of injury, injury associated vitreous hemorrhage, trauma associated RD, post traumatic RD, aphakia at injury, periocular trauma and OTS in cases of OGI. RESULTS: Totally 102 patients with traumatic OGI with a minimum of 12 mo follow-up and a median age at of 48.6 y(range: 3-104 y) were identified. Final best corrected visual acuity(BCVA) was independent from the time of repair, yet a statistically significant difference was present between the final BCVA and the zone of injury. Severe trauma presenting with an OTS score Ⅰ(P<0.0001) or Ⅱ(P<0.0001) revealed a significantly worse BCVA at last follow up when compared to the cohort with an OTS score >Ⅲ. OGI associated RD was observed in 36/102 patients(35.3%), whereas post traumatic RD(defined as RD following 14 d after OGI) occurred in 37 patients(36.3%). OGI associated RD did not correlate with the OTS and the zone of injury(P=0.193), yet post traumatic RD correlated significantly with zone Ⅲ injuries(P=0.013). CONCLUSION: The study shows a significant association between lower OTS score and zone Ⅲ injury with lower final BCVA and a higher number of surgeries, but only zone Ⅲ could be significantly associated with a higher rate of RD.

Measurement of Retinal Thickness in Normal Subjects with Retinal Thickness Analyzer

The retinal thickness at posterior pole of normal subjects was mea-sured by using retinal thickness analyzer (RTA) to determine the values of retinal thickness and to establish map of retinal thickness in normal subjects. The retina of 6 mm× 6 mm in size (approximately 20°, centered on the macula) at the poste-rior pole was scanned by using RTA to obtain images of 116 normal eyes of 77cases of various age group. The irnages were processed by a computer to obtain the retinal thickness values and the thickness map of this location. The data were analyzed with SAS software package. The mean retinal thickness was 171. 77±26. 13 pm with no significant difference among the various age groups (P>0. 05).The thickness maps of the retina of 6 mm× 6 mm size at the posterior pole around the macula rendered a 'U'-shaped pattern, extending from the disc to the superior and inferior of the fovea. The retina was found to be thin at temporal side of the fovea, with the thinnest area being at the macula central fovea. The U-shaped pattern of the retinal thickness maps was well in agreement with the topography of the ganglion cells and the retinal nerve fibers in human retina. The measurement of the retinal thickness by RTA reflected the changes in the layers of ganglion cells and the retinal nerve fiber. Each scanning session of RTA examination can yield multiple optical cross-section images of the retina and obtain retinal thickness maps of posterior pole of living eyes.

Preliminary Studies on the Application of Retinal Thickness Analyzer in the Diagnosis of Glaucoma

The patients with glaucoma underwent the examination of retinal thickness analyzer (RTA) to explore the diagnostic value of RTA in glaucoma. The retina of 6 mm×6 mm size (approximately 20°, centered on the macula) at the posterior pole was scanned by using RTA to obtain the images in 35 eyes of 22 patients with glaucoma. The images were processed by using SAS software package. The retinal thickness in the patients with glaucoma showed diffuse or local thinning. Twenty seven eyes was definitely diagnosed as having glaucoma. There was a very significant difference in retinal thickness measurements by RTA between normal group and glaucomatous group ( P =0.0012). Except the measurements at the detected point 6 having no difference, the measurements at the detected point 3 showed a significant difference and the remaining 7 detected points presented a very significant difference between the two groups. Of the detected 9 points, the changes at the points 4, 8, and 9 were the most obvious. The discrete analysis was performed on the glaucomatous patients by a discriminant function established through the data at the detected points 4, 8 and 9 and the accurate estimate rate for the diagnosis of glaucoma was up to 80.77 %. The measurements of RTA examination was consistent with the results of the vision field test. It was suggested that diffuse or local thinning of retinal thickness exists in the patients with glaucoma. The temporal inferior arcuate fibers and the papillomacular bundle between the macular and optic nerve heads showed a serious damage. The sensitivity of RTA examination was higher than visual field test.

Roles of the ocular pressure, pressure-sensitive ion channel, and elasticity in pressure-induced retinal diseases

The intraocular pressure inside the human eye maintains 10–21 mmHg above the atmospheric pressure.Elevation of intraocular pressure is highly correlated with the retinopathy in glaucoma,and changes in the exterior pressure during mountain hiking,air traveling,and diving may also induce vision decline and retinopathy.The pathophysiological mechanism of these pressure-induced retinal disorders has not been completely clear.Retinal neurons express pressure-sensitive channels intrinsically sensitive to pressure and membrane stretch,such as the transient receptor potential channel(TRP)family permeable to Ca^2+and Na^+and the two-pore domain K channel family.Recent data have shown that pressure excites the primate retinal bipolar cell by opening TRP vanilloid 4 to mediate transient depolarizing currents,and TRP vanilloid 4 agonists enhance the membrane excitability of primate retinal ganglion cells.The eyeball wall is constructed primarily by the sclera and cornea of low elasticity,and the flow rate of the aqueous humor and intraocular pressure both fluctuate,but the mathematical relationship between the ocular elasticity,aqueous humor volume,and intraocular pressure has not been established.This review will briefly review recent literature on the pressure-related retinal pathophysiology in glaucoma and other pressure-induced retinal disorders,the elasticity of ocular tissues,and pressure-sensitive cation channels in retinal neurons.Emerging data support the global volume and the elasticity and thickness of the sclera and cornea as variables to affect the intraocular pressure level like the volume of the aqueous humor.Recent results also suggest some potential routes for TRPs to mediate retinal ganglion cell dysfunction:TRP opening upon intraocular pressure elevation and membrane stretch,enhancing glutamate release from bipolar cells,increasing intracellular Na^+,Ca^2+concentration in retinal ganglion cells and extracellular glutamate concentration,inactivating voltage-gated Na^+channels,and causing excitotoxicity and dysfunction of retinal ganglion cells.Further studies on these routes likely identify novel targets and therapeutic strategies for the treatment of pressure-induced retinal disorders.

An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

Implementing different tools and injury mechanisms in multiple animal models of retina regeneration,researchers have discovered the existence of retinal stem/pro-genitor cells.Although they appear to be distributed uniformly across the vertebrate lineage,the reparative potential of the retina is mainly restricted to lower vertebrates.Regenerative repair post-injury requires the creation of a proliferative niche,vital for proper stem cell activation,propagation,and lineage differentiation.This seems to be lacking in mammals.Hence,in this review,we first discuss the many forms of retinal injuries that have been generated using animal models.Next,we discuss how they are utilized to stimulate regeneration and mimic eye disease pathologies.The key to driving stem cell activation in mammals relies on the information we can gather from these models.Lastly,we present a brief update about the genes,growth factors,and signaling pathways that have been brought to light using these models.

Tweaking the immune system as an adjuvant for the treatment of retinal degenerations

Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level,though the actual mechanism of repair still needs further investigations.The immune system responds in several ways upon photoreceptor engraftment,resulting in T-cell and macrophage infiltrations and,consequently,decrease in graft survival.Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting.Conversely,the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms.Here,Neves and colleagues explored the potential of cross-species studies and,to a certain extent,the concept of a protective immune system in retinal degeneration and therapy.Mesencephalic astrocyte-derived neurotrophic factor(MANF)was identified in this study as a novel factor that,by modulating the immune system,can slow down photoreceptor degeneration and improve transplantation outcome.

Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion

Retinal vein occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity (VA) in this retinal vascular disorder. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection route. The most widely injected drugs so far have been triamcinolone acetonide (TA) and bevacizumab. The objective of this review is to evaluate the evidence and discuss the rationale behind the recent suggestions that intravitreal pharmacotherapy by corticosteroids and anti-vascular endothelial growth factors may be useful in the treatment of retinal vein occlusion.