The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Dear Editor,Irreversible retinal damage can occur due to retinal degenerative(RD)diseases as well as injuries caused by accidents or devices.Laser devices can inflict permanent damage to the retina,leading to the loss...Dear Editor,Irreversible retinal damage can occur due to retinal degenerative(RD)diseases as well as injuries caused by accidents or devices.Laser devices can inflict permanent damage to the retina,leading to the loss of photoreceptors(PRs)and underlying retinal pigment epithelium(RPE),culminating in vision impairment.Since there is no effective treatment for permanent retinal injuries,replacing damaged PRs and RPE with corresponding healthy cells can be a suitable therapeutic approach.展开更多
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 contin...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.展开更多
This study presents a real-time tracking algorithm derived from the retina algorithm,designed for the rapid,real-time tracking of straight-line particle trajectories.These trajectories are detected by pixel detectors ...This study presents a real-time tracking algorithm derived from the retina algorithm,designed for the rapid,real-time tracking of straight-line particle trajectories.These trajectories are detected by pixel detectors to localize single-event effects in two-dimensional space.Initially,we developed a retina algorithm to track the trajectory of a single heavy ion and achieved a positional accuracy of 40μm.This was accomplished by analyzing trajectory samples from the simulations using a pixel sensor with a 72×72 pixel array and an 83μm pixel pitch.Subsequently,we refined this approach to create an iterative retina algorithm for tracking multiple heavy-ion trajectories in single events.This iterative version demonstrated a tracking efficiency of over 97%,with a positional resolution comparable to that of single-track events.Furthermore,it exhibits significant parallelism,requires fewer resources,and is ideally suited for implementation in field-programmable gate arrays on board-level systems,facilitating real-time online trajectory tracking.展开更多
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 thr...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%N_(2)),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.展开更多
Microcystin-LR(MC-LR)is a highly toxic category of biotoxins that can damage eye development and retinal structure in zebrafish,while probiotics can largely benefit the function of the retina.Although they both act on...Microcystin-LR(MC-LR)is a highly toxic category of biotoxins that can damage eye development and retinal structure in zebrafish,while probiotics can largely benefit the function of the retina.Although they both act on the visual system,whether probiotics can alleviate the visual damage caused by MC-LR in fish and the underlying mechanisms remains unclear.In this study,we exposed adult zebrafish for 28 days at MC-LR concentrations of 0,2.20,and 22.00μg/L with or without the probiotic Lactobacillus rhamnosus in the diet.MC-LR exposure alone resulted in structural damage to the retina and abnormal phototropic behavior,whereas L.rhamnosus could alleviate these damages.Biochemical analyses showed thatMCLR-induced abnormalities in apoptosis of ocular cells,retinal inflammatory responses,neurotransmission,and phototransduction were restored in the L.rhamnosus treatment group,indicating L.rhamnosus alleviated MC-LR-induced defects in the visual system and dysfunctions.This study underlines the defensive role of probiotics in protecting the host from environmental pollutants,which may provide guidance for the application of probiotics in aquaculture.展开更多
AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPAR...AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPARαknockout mice received either HFD or a standard diet(SD).A fluorometric method was used to determine the retinal triglycerides.The retinal malondialdehyde(MDA)content was measured.Hematoxylin-eosin was used to evaluate retinal pathological changes.Protein expression was analyzed by Western blot and immunofluorescence,while mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Electroretinogram was used to assess retinal function.RESULTS:HFD resulted in increased fatty acidβ-oxidation in the inner retina,particularly retinal ganglion cells(RGCs),as well as increased weight and accumulation of retinal triglyceride.Retinal fatty acid β-oxidation and triglyceride accumulation were affected by PPARα^(−/−)abnormalities.PPARαknockdown increased the infiltration and activation of inflammatory cells,as well as it upregulated the nuclear factor kappa B(NF-κB)signaling pathway and corresponding proinflammatory cytokine levels in the most retina subjected to the HFD.In the HFD mice,oxidative stress levels were elevated in the inner retina,particularly in the HFD PPARα^(−/−)mice.HFD-induced RGCs apoptosis initiation was exacerbated by PPARαdeficiency.Lastly,HFD feeding resulted in the lower amplitudes of scotopic a-wave,b-wave and photopic negative response(PhNR)wave,particularly in HFD PPARα^(−/−)mice.CONCLUSION:In HFD-fed mice retina,particularly in the inner retina,PPARα knockout increases lipid metabolic abnormalities,inflammatory responses,oxidative stress,apoptosis initiation and dysfunction.展开更多
Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investiga...Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.展开更多
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 inj...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.展开更多
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 subje...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.展开更多
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 un...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.展开更多
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 m...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.展开更多
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 pr...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.展开更多
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 ...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.展开更多
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 re...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.展开更多
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. Macul...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.展开更多
Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)mice.To investigate the effect of LBP on the reactivity o...Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)mice.To investigate the effect of LBP on the reactivity of retinal glial cells,an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mm Hg for 60 minutes.Either LBP solution(1 mg/kg)or phosphate-buffered saline was administrated to the mice by gavage daily,starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 post-insult.After AOH insult,increased numbers of astrocytes and microglia were observed,together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice:glial fibrillary acidic protein,glutamine synthetase,aquaporin-4,S-100 proteins,ionized calcium-binding adaptor molecule 1,amyloid precursor protein and receptor of advanced glycosylation end-products.After intervention with LBP,the above changes were significantly reduced.Remarkably,morphological remodeling of blood vessel-associated retinal astrocytes,marked by glial fibrillary acidic protein,was also observed.These results,taken together,suggest that LBP regulated the production of amyloid-βand expression of receptor of advanced glycosylation end-products,as well as mediating the activity of retinal glial cells,which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH insult.This study was approved by the Committee for the Use of Live Animals in Teaching and Research(approval No.CULTRA-#1664-08).展开更多
Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the de...Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.展开更多
AIM: To evaluate baseline foveal disorganisation of retinal inner layers(DRIL) as a prognostic factor in eyes with central retinal artery occlusion(CRAO). METHODS: Twenty-eight CRAO patients who were followed-up betwe...AIM: To evaluate baseline foveal disorganisation of retinal inner layers(DRIL) as a prognostic factor in eyes with central retinal artery occlusion(CRAO). METHODS: Twenty-eight CRAO patients who were followed-up between 2010 and 2016 were retrospectively investigated. Demographic characteristics and detailed ophthalmological examination findings of all patients were recorded. Macular thicknesses(MTs) from 5 separate spots and DRIL were measured with spectral-domain optic coherence tomography(SD-OCT). Correlations between DRIL score and logMAR converted visual acuity(VA), change in VA, patient reference time(RT), number of hyperbaric oxygen therapy(HBOT) sessions, MT and MT change were investigated.RESULTS: There was a positive correlation between the DRIL score and the final VA(r=0.787) and a negative correlation with the change in VA(r=-0.763). The RT and MT were closely related to the DRIL score. A negative correlation was found between the number of HBOT sessions and the DRIL score(r=-0.341).CONCLUSION: The DRIL score is a parameter assessed by SD-OCT, which can provide us reliable information regarding the prognosis of visual functions and response to the treatment for CRAO patients at acute phase.展开更多
AIM： To characterize the pattern of intraocular pressure （lOP） change and the deficit of retinal ganglion cells （RGCs） in DBA2J, which is most well-characterized chronic glaucoma mouse model and wild type （WT） ...AIM： To characterize the pattern of intraocular pressure （lOP） change and the deficit of retinal ganglion cells （RGCs） in DBA2J, which is most well-characterized chronic glaucoma mouse model and wild type （WT） C57bl/6 mice, and to study the relationship between lOP change and RGCs deficit. METHODS： lOP was monitored with a rebound tonometer in C57bl/6 and DBA2J mice from 3 to 15-month-old. Retinal function was evaluated by dark -adapted electroretinogram （ERG） in DBA2J and WT mice of 15-month-old. A dye （Neurobiotin） was applied to optic nerve stump to retrograde label RGCs. TO-PRO-3 visualized all nuclei of cells in the RGC layer. RESULTS： The lOP in WT mice was 9.03-0.6 mm Hg on average and did not increase significantly as aging. The lOP in DBA2J mice, arranging from 7.2 to 28 mm Hg, was increasing significantly as aging, and it was normal at 3-month--old compared with WT mice, slightly increased from 7-month-old and increased in 50% animals at 11-month-old and in 38% animals at 15-month-old. The RGCs density in DBA2J mice started reducing by 7-month-old, continuously decreased until reached about 20% of RGC in WT retina by 15-month-old. RGC density was not linearly correlated with lOP in 15-month- old DBA2J mice. The amplitude of positive scotopic threshold response, and negative scotopic threshold response of ERG were significantly reduced in DBA2J mice of 15-month-old than that in age-paired WT mice. CONCLUSION： The present study found that DBA2J mice display pathological and functional deficits of the retina that was not linearly correlated with lOP.展开更多
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the National Eye Institute,National Institute of Health,Bethesda,Maryland,USA[CIRM DISC1-09912(BBT),NIH EY031144(BBT),R01 EY031834,EY-017337]the USC Ophthalmology Core(NIH P30EY029220,an unrestricted grant to the USC Department of Ophthalmology from RPB)+1 种基金the BrightFocus Foundation(M2016186,BBT)support from a Research to Prevent Blindness(RPB,New York,NY,USA)unrestricted grant to the UCI Department of Ophthalmology.
文摘Dear Editor,Irreversible retinal damage can occur due to retinal degenerative(RD)diseases as well as injuries caused by accidents or devices.Laser devices can inflict permanent damage to the retina,leading to the loss of photoreceptors(PRs)and underlying retinal pigment epithelium(RPE),culminating in vision impairment.Since there is no effective treatment for permanent retinal injuries,replacing damaged PRs and RPE with corresponding healthy cells can be a suitable therapeutic approach.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘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.
基金supported by the National Natural Science Foundation of China(No.12205224)the Research Foundation of Education Bureau of Hubei Province China(No.Q20221703)+1 种基金the National Natural Science Foundation of China(Nos.12035006,U2032140)the National Key Research and Development Program of China(No.2020YFE0202000)。
文摘This study presents a real-time tracking algorithm derived from the retina algorithm,designed for the rapid,real-time tracking of straight-line particle trajectories.These trajectories are detected by pixel detectors to localize single-event effects in two-dimensional space.Initially,we developed a retina algorithm to track the trajectory of a single heavy ion and achieved a positional accuracy of 40μm.This was accomplished by analyzing trajectory samples from the simulations using a pixel sensor with a 72×72 pixel array and an 83μm pixel pitch.Subsequently,we refined this approach to create an iterative retina algorithm for tracking multiple heavy-ion trajectories in single events.This iterative version demonstrated a tracking efficiency of over 97%,with a positional resolution comparable to that of single-track events.Furthermore,it exhibits significant parallelism,requires fewer resources,and is ideally suited for implementation in field-programmable gate arrays on board-level systems,facilitating real-time online trajectory tracking.
基金Supported by the Tianjin Health Research Project(No.ZC20069No.TJWJ2022MS040)+1 种基金the Foundation of the Committee of Integrated Traditional Chinese and Western Medicine(No.2021011)the Science and Technology Foundation of Tianjin Eye Hospital(No.YKYB1901).
文摘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%N_(2)),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.
基金supported by the National Key Research and Development Program of China(No.2023YFD2400900)the National Natural Science Foundation of China(Nos.32171619 and 32201388)+2 种基金the Youth project of the Natural Science Foundation of Hubei Province(No.2021CFB243)Hubei Province Excellent Young and Middle aged Science and Technology Innovation Team Project(No.T2022028)the Youth Talent Project of Science and Technology Research Program of Hubei Provincial Department of Education(No.Q20212503)。
文摘Microcystin-LR(MC-LR)is a highly toxic category of biotoxins that can damage eye development and retinal structure in zebrafish,while probiotics can largely benefit the function of the retina.Although they both act on the visual system,whether probiotics can alleviate the visual damage caused by MC-LR in fish and the underlying mechanisms remains unclear.In this study,we exposed adult zebrafish for 28 days at MC-LR concentrations of 0,2.20,and 22.00μg/L with or without the probiotic Lactobacillus rhamnosus in the diet.MC-LR exposure alone resulted in structural damage to the retina and abnormal phototropic behavior,whereas L.rhamnosus could alleviate these damages.Biochemical analyses showed thatMCLR-induced abnormalities in apoptosis of ocular cells,retinal inflammatory responses,neurotransmission,and phototransduction were restored in the L.rhamnosus treatment group,indicating L.rhamnosus alleviated MC-LR-induced defects in the visual system and dysfunctions.This study underlines the defensive role of probiotics in protecting the host from environmental pollutants,which may provide guidance for the application of probiotics in aquaculture.
基金Supported by the Anhui Medical University Research Fund(No.2023xkj035)National Natural Science Foundation Incubation Program Project of the Second Affiliated Hospital of Anhui Medical University(No.2023GQFY05)the Key Research and Development Technology project of Anhui Province(No.2022j11020013).
文摘AIM:To examined the effects of a high-fat diet(HFD)on retinal pathological changes and dysfunction using peroxisome proliferator-activated receptor-alpha(PPARα)knockout mice.METHODS:For four months,C57BL/6J and PPARαknockout mice received either HFD or a standard diet(SD).A fluorometric method was used to determine the retinal triglycerides.The retinal malondialdehyde(MDA)content was measured.Hematoxylin-eosin was used to evaluate retinal pathological changes.Protein expression was analyzed by Western blot and immunofluorescence,while mRNA expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Electroretinogram was used to assess retinal function.RESULTS:HFD resulted in increased fatty acidβ-oxidation in the inner retina,particularly retinal ganglion cells(RGCs),as well as increased weight and accumulation of retinal triglyceride.Retinal fatty acid β-oxidation and triglyceride accumulation were affected by PPARα^(−/−)abnormalities.PPARαknockdown increased the infiltration and activation of inflammatory cells,as well as it upregulated the nuclear factor kappa B(NF-κB)signaling pathway and corresponding proinflammatory cytokine levels in the most retina subjected to the HFD.In the HFD mice,oxidative stress levels were elevated in the inner retina,particularly in the HFD PPARα^(−/−)mice.HFD-induced RGCs apoptosis initiation was exacerbated by PPARαdeficiency.Lastly,HFD feeding resulted in the lower amplitudes of scotopic a-wave,b-wave and photopic negative response(PhNR)wave,particularly in HFD PPARα^(−/−)mice.CONCLUSION:In HFD-fed mice retina,particularly in the inner retina,PPARα knockout increases lipid metabolic abnormalities,inflammatory responses,oxidative stress,apoptosis initiation and dysfunction.
基金supported by the National Natural Science Foundation of China,Nos.81970820(to HX),31771644(to JL),31930068(to JL),82371176(to JL),81801331(to LC)National Key Research and Development Project of China.Nos.2017YFA0104100(to JL),2017YFA0701304(to HX)+1 种基金Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)Talent Introduction Plan,No.KYPT202204(to LC)the Fundamental Research Funds for the Central Universities,No.22120230292(to JL)。
文摘Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.
文摘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.
文摘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.
基金Part of the review is supported by the Ramalingaswami award to SPH and grant received from DBT,Govt of India(BT/HRD/35/02/2006).RDS is recipient of junior research fellowships from CSIR,Govt.of India(09/028(1146)/2020-EMR-I).
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China,No.82371051(to DW)the Natural Science Foundation of Beijing,No.7212092(to DW)+1 种基金the Capital’s Funds for Health Improvement and Research,No.2022-2-5041(to DW)the Fund of Science and Technology Development of Beijing Rehabilitation Hospital,Capital Medical University,No.2021R-001(to YL).
文摘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.
文摘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.
文摘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.
基金supported in part by the National Basic Research Program of China,No.81300766(to XSM)the Cultivation and Innovation Fund from the First Affiliated Hospital of Jinan University,China,No.802168(to XSM)+2 种基金Hygiene&Health Appropriated Technology and Promoting Project of Guangdong Province of China,No.201905270933056876(to XSM)the fund of Leading Talents of Guangdong Province of China,No.87014002(to KFS)a grant from Ningxia Key Research and Development Program,and Programme of Introducing Talents of Discipline to Universities of China,No.B14036(to KFS)。
文摘Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)mice.To investigate the effect of LBP on the reactivity of retinal glial cells,an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mm Hg for 60 minutes.Either LBP solution(1 mg/kg)or phosphate-buffered saline was administrated to the mice by gavage daily,starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 post-insult.After AOH insult,increased numbers of astrocytes and microglia were observed,together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice:glial fibrillary acidic protein,glutamine synthetase,aquaporin-4,S-100 proteins,ionized calcium-binding adaptor molecule 1,amyloid precursor protein and receptor of advanced glycosylation end-products.After intervention with LBP,the above changes were significantly reduced.Remarkably,morphological remodeling of blood vessel-associated retinal astrocytes,marked by glial fibrillary acidic protein,was also observed.These results,taken together,suggest that LBP regulated the production of amyloid-βand expression of receptor of advanced glycosylation end-products,as well as mediating the activity of retinal glial cells,which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH insult.This study was approved by the Committee for the Use of Live Animals in Teaching and Research(approval No.CULTRA-#1664-08).
基金supported by the National Natural Science Foundation of China,No.30771140,31070952 and U1204311
文摘Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.
文摘AIM: To evaluate baseline foveal disorganisation of retinal inner layers(DRIL) as a prognostic factor in eyes with central retinal artery occlusion(CRAO). METHODS: Twenty-eight CRAO patients who were followed-up between 2010 and 2016 were retrospectively investigated. Demographic characteristics and detailed ophthalmological examination findings of all patients were recorded. Macular thicknesses(MTs) from 5 separate spots and DRIL were measured with spectral-domain optic coherence tomography(SD-OCT). Correlations between DRIL score and logMAR converted visual acuity(VA), change in VA, patient reference time(RT), number of hyperbaric oxygen therapy(HBOT) sessions, MT and MT change were investigated.RESULTS: There was a positive correlation between the DRIL score and the final VA(r=0.787) and a negative correlation with the change in VA(r=-0.763). The RT and MT were closely related to the DRIL score. A negative correlation was found between the number of HBOT sessions and the DRIL score(r=-0.341).CONCLUSION: The DRIL score is a parameter assessed by SD-OCT, which can provide us reliable information regarding the prognosis of visual functions and response to the treatment for CRAO patients at acute phase.
基金Supported by International Retinal Research Foundation
文摘AIM： To characterize the pattern of intraocular pressure （lOP） change and the deficit of retinal ganglion cells （RGCs） in DBA2J, which is most well-characterized chronic glaucoma mouse model and wild type （WT） C57bl/6 mice, and to study the relationship between lOP change and RGCs deficit. METHODS： lOP was monitored with a rebound tonometer in C57bl/6 and DBA2J mice from 3 to 15-month-old. Retinal function was evaluated by dark -adapted electroretinogram （ERG） in DBA2J and WT mice of 15-month-old. A dye （Neurobiotin） was applied to optic nerve stump to retrograde label RGCs. TO-PRO-3 visualized all nuclei of cells in the RGC layer. RESULTS： The lOP in WT mice was 9.03-0.6 mm Hg on average and did not increase significantly as aging. The lOP in DBA2J mice, arranging from 7.2 to 28 mm Hg, was increasing significantly as aging, and it was normal at 3-month--old compared with WT mice, slightly increased from 7-month-old and increased in 50% animals at 11-month-old and in 38% animals at 15-month-old. The RGCs density in DBA2J mice started reducing by 7-month-old, continuously decreased until reached about 20% of RGC in WT retina by 15-month-old. RGC density was not linearly correlated with lOP in 15-month- old DBA2J mice. The amplitude of positive scotopic threshold response, and negative scotopic threshold response of ERG were significantly reduced in DBA2J mice of 15-month-old than that in age-paired WT mice. CONCLUSION： The present study found that DBA2J mice display pathological and functional deficits of the retina that was not linearly correlated with lOP.
