Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.展开更多
AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal de...AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal detachment(RRD).METHODS:A total of 58 eligible patients were enrolled and randomly assigned to two groups based on tamponade duration:the short-term group(30-45d)and the conventional group(≥90d).Comprehensive evaluations were performed before and after SOR,including slitlamp examination,best-corrected visual acuity(BCVA)measurement,intraocular pressure(IOP)testing,optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),microperimetry,electroretinography(ERG),and visual evoked potential(VEP)assessment.RESULTS:A total of 33 patients(23 males and 10 females;33 eyes)were enrolled in the short-term SO tamponade group with mean age of 52.45±9.35y,and 25 patients(15 males and 10 females;25 eyes)were enrolled in the conventional SO tamponade group with mean age of 50.80±12.06y.Compared with the conventional group,the short-term silicone oil tamponade group had a significantly lower incidence of silicone oil emulsification and cataract progression,with no significant difference in retinal reattachment success rate.Structurally,short-term tamponade was associated with increased thickness of the retinal ganglion cell layer(RGCL)in the nasal and superior macular regions and improved recovery of superficial retinal vascular density in these areas.Functionally,the shortterm group showed better BCVA and retinal sensitivity both before and 1mo after SOR;additionally,the P100 amplitude in VEP tests was significantly increased in this group.CONCLUSION:Shortening the duration of silicone oil tamponade effectively reduces damage to retinal structure and function without compromising the success rate of retinal reattachment in patients with primary RRD.展开更多
Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response...The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response fails to restore endoplasmic reticulum homeostasis,it can trigger proinflammatory and pro-death signals,which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases.This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases.The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise.Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies,including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid,which enhance protein folding and reduce endoplasmic reticulum stress.Small molecule modulators that influence endoplasmic reticulum stress sensors,including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1,are also potential therapeutic agents.Additionally,inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1,a key endoplasmic reticulum stress sensor,represent another class of drugs that could prevent the formation of toxic aggregates.The activation of nuclear receptors,such as PPAR and FXR,may also help mitigate ER stress.Furthermore,enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins.Combination treatments that involve endoplasmicreticulum-stress-targeting drugs and gene therapies are also being explored.Despite these potential therapeutic strategies,significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration,and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective,well-tolerated drugs.The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects,which have hindered their clinical translation.Moreover,signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance.Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies.In conclusion,while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases,additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central n...Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.展开更多
The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmento...The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.展开更多
Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatm...Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.展开更多
AIM:To investigate the underlying causes of surgical failure and reoperation management in patients with rhegmatogenous retinal detachment(RRD)who underwent scleral buckle surgery at our institution.METHODS:This was a...AIM:To investigate the underlying causes of surgical failure and reoperation management in patients with rhegmatogenous retinal detachment(RRD)who underwent scleral buckle surgery at our institution.METHODS:This was a single-center,retrospective,descriptive study.The clinical data of 368 patients(387 eyes)with RRD who underwent scleral buckling(SB)surgery between August 2013 and July 2023 at our institution were collected.The aim was to analyze the causes of recurrence and the rationale for selecting reoperation methods.RESULTS:Totally 368 patients(387 eyes)were included in the analysis,comprising 222 males and 146 females.The average age was 30.26±14.18 years,and the mean follow-up duration was(48.33±20.39)mo.The success rate of SB surgery was 90.2%.Recurrent retinal detachment occurred in 38 eyes.Based on surgical records,the causes of SB failure were analyzed.The recurrence causes included abnormal compression ridge position(position,height,or width)in 14 eyes(36.8%,14/38),hole omission in 11 eyes(29.0%,11/38),proliferative vitreoretinopathy(PVR)in 10 eyes(26.3%,10/38),and new holes in 3 eyes(7.9%,3/38).Among these,8 eyes(21.1%,8/38)underwent repeat SB surgery,while the remaining 30 eyes(78.9%,30/38)underwent pars plana vitrectomy(PPV).Regarding tamponade agents,silicone oil was used in 11 eyes(36.7%,11/30),C 3F 8 gas in 12 eyes(40.0%,12/30),and sterile air in 7 eyes(23.3%,7/30).CONCLUSION:SB surgery demonstrates a high success rate in the treatment of RRD.However,abnormal compression ridge position,missed holes during surgery,and PVR are the primary causes of SB failure.After addressing the reasons for failure,re-SB surgery or PPV can be effective alternatives.展开更多
Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 199...Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 1993.TM typically spares the foveal center,is asymptomatic,and is often detected incidentally during routine ophthalmic examinations.Through literature search,we did not identify racial or regional differences in TM.It predominantly affects children,with an estimated prevalence of 2 per 100000 in individuals under 16 ages[3].While previous reports have focused on pediatric and adult populations,this study presents four cases of TM in preterm infants.展开更多
AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included ...AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1,2017,to March 31,2022.Data on disease duration,age,hypertension,OCT images,central macular thickness(CMT),and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment.Patients were divided into 4 groups according to different types of macular edema:cystoid macular edema(CME),sponge-like diffuse retinal thickening(SDRT),serous retinal detachment(SRD),and mixed type(FULL).Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types,and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS:Totally 139 patients(139 eyes)were classified as having macular edema,including 62 males(44.6%)and 77 females(55.4%),with a mean age of 58.9±10.9 years,and they were divided into 4 groups based on different types of macular edema,including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group,23 cases(23 eyes;mean age 56.6±10.2 years)in the SDRT group,22 cases(22 eyes;mean age 57.8±12.0 years)in the SDR group,and 40 cases(40 eyes;mean age 60.0±10.7 years)in the FULL group.There were no significant differences in the duration of disease or age between groups(P>0.05).There was a significant difference in preoperative CMT between groups(P=0.01,one-way ANOVA),with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03).There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26).After conbercept treatment,the macular central recess thickness was reduced and visual acuity was improved in all four groups,among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05),and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05).Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images,in which the efficacy is best in patients with CME but poor in patients with SDRT.展开更多
Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown ...Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.展开更多
AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCT...AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.展开更多
Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of n...Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of neurodegenerative diseases with glaucoma being highly prevalent.Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells and their axons which make up the optic nerve.It is the leading cause of irreversible vision loss and affects an estimated 80 million people.The mammalian central nervous system is non-regenerative and,once lost or injured,retinal ganglion cells cannot regenerate an axon into the optic nerve under basal conditions.Thus,strategies that provide neuroprotection to stressed,dysfunctional,or dying retinal ganglion cells are likely to be of high therapeutic and translational value.Advancing age,genetics,and elevated intraocular pressure are all major risk factors for glaucoma,however,all clinically available glaucoma treatments focus on intraocular pressure management and do not directly address the neurodegenerative component of glaucoma.展开更多
Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellula...Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellular mechanisms,including inflammation,cell migration,and the activation of proliferative signaling pathways.One of the most challenging complications of RRD is proliferative vitreoretinopathy(PVR),which refers to the proliferation and contraction of fibrocellular membranes on the retinal surface and in the vitreous cavity.PVR is a major cause of surgical failure in RRD,as it can lead to recurrent retinal detachment and severe vision loss.However,the pathogenesis of PVR is not yet fully understood,and the treatment options are quite limited.Recent advances in analytical techniques have offered valuable insights into the molecular alterations present in the subretinal fluid(SRF)of patients with RRD.This review seeks to consolidate the current knowledge regarding the SRF profile in RRD and PVR,emphasizing potential biomarkers and therapeutic targets.展开更多
AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This o...AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This observational clinical study utilized a cross-sectional and prospective design,focusing on chronic alcohol consumers alongside a non-consuming control group.OCT/OCTA imaging parameters including central retinal subfield thickness(CST),subfoveal choroidal thickness(SCT),foveal avascular zone(FAZ)and vessel density(VD)in the superficial and deep capillary plexuses in both the macular and optic disc(OD)regions were recorded.Data were analyzed using SPSS 15.0;descriptive statistics were reported,group comparisons were performed with Chisquare,Kruskal–Wallis,and Bonferroni-corrected Mann–Whitney U tests,and relationships were assessed using Spearman correlation,with statistical significance set at P<0.05.RESULTS:A total of 160 eyes of 160 participants(110 females and 50 males with mean age 38.7±9.9y)who don’t smoke were divided into five groups:never,occasional,monthly,weekly and daily drinkers.The mean CST was 216.6±14.2μm and the mean SCT was 358.9±84.5μm.There was no statistically significantly difference in CST and SCT among the groups(P=0.890,0.799).Foveal superficial capillary plexuses(SCPs)VD was higher in monthly drinkers compared to occasional drinkers(P=0.015).Foveal VD in deep capillary plexus was also higher in monthly drinkers than in never and occasional drinkers(P=0.004,0.006).Nasal SCPs VD at the OD was higher in monthly drinkers compared to never drinkers(P=0.005).There was no significant difference FAZ area among the groups(P=0.071).CONCLUSION:Both superficial and deep microvascular structures in the inferior quadrants of macula are positively correlated with frequency of alcohol use.Also in our study results is that the monthly drinker group has uniquely higher VDs in both macula and OD.This leads us to consider moderate alcohol consumption may also have protective effects on retinal microcirculation.展开更多
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
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
基金Supported by the Key Science&Technology Project of Guangzhou(No.202103000045)the National Natural Science Foundation of China(No.82070972,No.82271093).
文摘AIM:To investigate the effects of shortening the duration of silicone oil tamponade on retinal structure and function in patients undergoing silicone oil removal(SOR)after surgery for primary rhegmatogenous retinal detachment(RRD).METHODS:A total of 58 eligible patients were enrolled and randomly assigned to two groups based on tamponade duration:the short-term group(30-45d)and the conventional group(≥90d).Comprehensive evaluations were performed before and after SOR,including slitlamp examination,best-corrected visual acuity(BCVA)measurement,intraocular pressure(IOP)testing,optical coherence tomography(OCT),optical coherence tomography angiography(OCTA),microperimetry,electroretinography(ERG),and visual evoked potential(VEP)assessment.RESULTS:A total of 33 patients(23 males and 10 females;33 eyes)were enrolled in the short-term SO tamponade group with mean age of 52.45±9.35y,and 25 patients(15 males and 10 females;25 eyes)were enrolled in the conventional SO tamponade group with mean age of 50.80±12.06y.Compared with the conventional group,the short-term silicone oil tamponade group had a significantly lower incidence of silicone oil emulsification and cataract progression,with no significant difference in retinal reattachment success rate.Structurally,short-term tamponade was associated with increased thickness of the retinal ganglion cell layer(RGCL)in the nasal and superior macular regions and improved recovery of superficial retinal vascular density in these areas.Functionally,the shortterm group showed better BCVA and retinal sensitivity both before and 1mo after SOR;additionally,the P100 amplitude in VEP tests was significantly increased in this group.CONCLUSION:Shortening the duration of silicone oil tamponade effectively reduces damage to retinal structure and function without compromising the success rate of retinal reattachment in patients with primary RRD.
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
文摘Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金supported by the Natural Science Foundation of Shaanxi Province(Key Program),No.2021JZ-60(to HZ)。
文摘The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins.However,if the unfolded protein response fails to restore endoplasmic reticulum homeostasis,it can trigger proinflammatory and pro-death signals,which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases.This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases.The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise.Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies,including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid,which enhance protein folding and reduce endoplasmic reticulum stress.Small molecule modulators that influence endoplasmic reticulum stress sensors,including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1,are also potential therapeutic agents.Additionally,inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1,a key endoplasmic reticulum stress sensor,represent another class of drugs that could prevent the formation of toxic aggregates.The activation of nuclear receptors,such as PPAR and FXR,may also help mitigate ER stress.Furthermore,enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins.Combination treatments that involve endoplasmicreticulum-stress-targeting drugs and gene therapies are also being explored.Despite these potential therapeutic strategies,significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration,and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective,well-tolerated drugs.The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects,which have hindered their clinical translation.Moreover,signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance.Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies.In conclusion,while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases,additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
基金supported by the Deutsche Forschungsgemeinschaft(DFG)with grants PR1569/1-1 and PR 1569/1-3(to VP).
文摘Globally,glaucoma stands as a primary cause of irreversible blindness,marked by intricate pathophysiological processes in which neuroinflammation plays a pivotal role.As the principal immune cells within the central nervous system,microglia play a dual function in the progression of glaucoma.Under standard physiological states,microglia safeguard the retina by offering neurotrophic support and removing cellular debris.In the pathological progression of glaucoma,microglia become activated and release significant levels of inflammatory factors,resulting in retinal ganglion cell injury,cell death,and impaired neuroregeneration.This review focuses on examining the dual functions of microglia in glaucoma,evaluating their influence on retinal neurodegeneration and repair,and suggesting that modulating microglial activity could serve as a promising therapeutic strategy.Understanding the mechanisms of microglial action in glaucoma is crucial for unveiling the complex pathophysiological processes of the disease and developing new therapeutic strategies.
基金Fundação de AmparoàPesquisa do Estado de São Paulo(FAPESP,Brazil,#2020/11667-0)and Universidade Federal do ABC(UFABC,Brazil)were recipients of fellowships from FAPESP:THLV(#2021/11969-9 and#2024/00828-3),GBS(#2021/14227-3),and GMB(#2024/10858-7)+1 种基金recipients of fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Brazil):MIM(Finance Code 001,#88887.597402/2021-00)recipients of fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Brazil.):GKD(#145164/2024-1),and DRA(#308819/2022-5).
文摘The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.
基金supported by a Ph.D.scholarship from the YLSY program of the Republic of Turkiye,Ministry of National Educationfunded by Fight for Sight UK,grant reference#5183/5184。
文摘Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.
文摘AIM:To investigate the underlying causes of surgical failure and reoperation management in patients with rhegmatogenous retinal detachment(RRD)who underwent scleral buckle surgery at our institution.METHODS:This was a single-center,retrospective,descriptive study.The clinical data of 368 patients(387 eyes)with RRD who underwent scleral buckling(SB)surgery between August 2013 and July 2023 at our institution were collected.The aim was to analyze the causes of recurrence and the rationale for selecting reoperation methods.RESULTS:Totally 368 patients(387 eyes)were included in the analysis,comprising 222 males and 146 females.The average age was 30.26±14.18 years,and the mean follow-up duration was(48.33±20.39)mo.The success rate of SB surgery was 90.2%.Recurrent retinal detachment occurred in 38 eyes.Based on surgical records,the causes of SB failure were analyzed.The recurrence causes included abnormal compression ridge position(position,height,or width)in 14 eyes(36.8%,14/38),hole omission in 11 eyes(29.0%,11/38),proliferative vitreoretinopathy(PVR)in 10 eyes(26.3%,10/38),and new holes in 3 eyes(7.9%,3/38).Among these,8 eyes(21.1%,8/38)underwent repeat SB surgery,while the remaining 30 eyes(78.9%,30/38)underwent pars plana vitrectomy(PPV).Regarding tamponade agents,silicone oil was used in 11 eyes(36.7%,11/30),C 3F 8 gas in 12 eyes(40.0%,12/30),and sterile air in 7 eyes(23.3%,7/30).CONCLUSION:SB surgery demonstrates a high success rate in the treatment of RRD.However,abnormal compression ridge position,missed holes during surgery,and PVR are the primary causes of SB failure.After addressing the reasons for failure,re-SB surgery or PPV can be effective alternatives.
基金Supported by the National Natural Science Foundation of China(No.82070991).
文摘Dear Editor,Torpedo maculopathy(TM),first described by Roseman and Gass in 1992[1],is a rare congenital unilateral retinal pigment epithelium(RPE)abnormality.The term“torpedo maculopathy”was coined by Daily[2]in 1993.TM typically spares the foveal center,is asymptomatic,and is often detected incidentally during routine ophthalmic examinations.Through literature search,we did not identify racial or regional differences in TM.It predominantly affects children,with an estimated prevalence of 2 per 100000 in individuals under 16 ages[3].While previous reports have focused on pediatric and adult populations,this study presents four cases of TM in preterm infants.
文摘AIM:To analyze the effect of conbercept treatment on different types of macular edema secondary to retinal vein occlusion(RVO-ME)using optical coherence tomography(OCT)images.METHODS:This retrospective study included patients who first received conbercept injections for RVO-ME at Yijishan Hospital of Wannan Medical College from December 1,2017,to March 31,2022.Data on disease duration,age,hypertension,OCT images,central macular thickness(CMT),and best-corrected visual acuity(BCVA)were collected before and at 4-6 wk after treatment.Patients were divided into 4 groups according to different types of macular edema:cystoid macular edema(CME),sponge-like diffuse retinal thickening(SDRT),serous retinal detachment(SRD),and mixed type(FULL).Changes in CMT and visual acuity before and after treatment were compared among the groups to analyze differences in the effect of conbercept treatment on different ME types,and the effect of baseline CMT and visual acuity on post-treatment visual acuity.RESULTS:Totally 139 patients(139 eyes)were classified as having macular edema,including 62 males(44.6%)and 77 females(55.4%),with a mean age of 58.9±10.9 years,and they were divided into 4 groups based on different types of macular edema,including 54 cases(54 eyes)(mean age 59.6±11.1 years)in the CME group,23 cases(23 eyes;mean age 56.6±10.2 years)in the SDRT group,22 cases(22 eyes;mean age 57.8±12.0 years)in the SDR group,and 40 cases(40 eyes;mean age 60.0±10.7 years)in the FULL group.There were no significant differences in the duration of disease or age between groups(P>0.05).There was a significant difference in preoperative CMT between groups(P=0.01,one-way ANOVA),with the CMT in the FULL group being significantly greater than that in the SDRT group(P=0.03).There were no significant differences in pre-treatment visual acuity between the four groups(P=0.26).After conbercept treatment,the macular central recess thickness was reduced and visual acuity was improved in all four groups,among which the CMT in the CME and FULL groups was reduced significantly compared with the other two groups(P<0.05),and the visual acuity in the CME and SRD groups was improved significantly compared with the other two groups(P<0.05).Postoperative visual acuity was negatively correlated with preoperative CMT(P=0.044)and positively correlated with preoperative visual acuity(P<0.01).CONCLUSION:The efficacy of intravitreal conbercept in the treatment of RVO and macular edema may be related to the type of edema observed on OCT images,in which the efficacy is best in patients with CME but poor in patients with SDRT.
基金supported by the National Natural Science Foundation of China,Nos.82471123,82171053the Jilin Province Special Project for Talent in Medical and Health Sciences,No.2024WSXK-E01the Natural Science Foundation of Jilin Province,YDZJ202501ZYTS318(all to GL).
文摘Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.
基金Central High-Level Traditional Chinese Medicine Hospital Project of Eye Hospital China Academy of Chinese Medical Science(No.GSP5-83,No.GSP4-02No.GSP5-06)+1 种基金Supported by National Natural Science Foundation of China(General ProgramNo.82474582).
文摘AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.
基金supported by St.Erik Eye Hospital philanthropic donations,Vetenskapsrådet 2022-00799(to PAW).
文摘Neurodegenerative diseases account for a large and increasing health and economic burden worldwide.With an increasingly aged population,this burden is set to increase.Optic neuropathies make up a large proportion of neurodegenerative diseases with glaucoma being highly prevalent.Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells and their axons which make up the optic nerve.It is the leading cause of irreversible vision loss and affects an estimated 80 million people.The mammalian central nervous system is non-regenerative and,once lost or injured,retinal ganglion cells cannot regenerate an axon into the optic nerve under basal conditions.Thus,strategies that provide neuroprotection to stressed,dysfunctional,or dying retinal ganglion cells are likely to be of high therapeutic and translational value.Advancing age,genetics,and elevated intraocular pressure are all major risk factors for glaucoma,however,all clinically available glaucoma treatments focus on intraocular pressure management and do not directly address the neurodegenerative component of glaucoma.
文摘Rhegmatogenous retinal detachment(RRD)is a serious ocular condition marked by the separation of the neuroretina from the retinal pigment epithelium(RPE).The pathogenesis of RRD involves intricate molecular and cellular mechanisms,including inflammation,cell migration,and the activation of proliferative signaling pathways.One of the most challenging complications of RRD is proliferative vitreoretinopathy(PVR),which refers to the proliferation and contraction of fibrocellular membranes on the retinal surface and in the vitreous cavity.PVR is a major cause of surgical failure in RRD,as it can lead to recurrent retinal detachment and severe vision loss.However,the pathogenesis of PVR is not yet fully understood,and the treatment options are quite limited.Recent advances in analytical techniques have offered valuable insights into the molecular alterations present in the subretinal fluid(SRF)of patients with RRD.This review seeks to consolidate the current knowledge regarding the SRF profile in RRD and PVR,emphasizing potential biomarkers and therapeutic targets.
文摘AIM:To investigate the effects of chronic alcohol consumption on retinal microcirculation by comparing different alcohol-consuming groups using optical coherence tomography(OCT)and OCT angiography(OCTA).METHODS:This observational clinical study utilized a cross-sectional and prospective design,focusing on chronic alcohol consumers alongside a non-consuming control group.OCT/OCTA imaging parameters including central retinal subfield thickness(CST),subfoveal choroidal thickness(SCT),foveal avascular zone(FAZ)and vessel density(VD)in the superficial and deep capillary plexuses in both the macular and optic disc(OD)regions were recorded.Data were analyzed using SPSS 15.0;descriptive statistics were reported,group comparisons were performed with Chisquare,Kruskal–Wallis,and Bonferroni-corrected Mann–Whitney U tests,and relationships were assessed using Spearman correlation,with statistical significance set at P<0.05.RESULTS:A total of 160 eyes of 160 participants(110 females and 50 males with mean age 38.7±9.9y)who don’t smoke were divided into five groups:never,occasional,monthly,weekly and daily drinkers.The mean CST was 216.6±14.2μm and the mean SCT was 358.9±84.5μm.There was no statistically significantly difference in CST and SCT among the groups(P=0.890,0.799).Foveal superficial capillary plexuses(SCPs)VD was higher in monthly drinkers compared to occasional drinkers(P=0.015).Foveal VD in deep capillary plexus was also higher in monthly drinkers than in never and occasional drinkers(P=0.004,0.006).Nasal SCPs VD at the OD was higher in monthly drinkers compared to never drinkers(P=0.005).There was no significant difference FAZ area among the groups(P=0.071).CONCLUSION:Both superficial and deep microvascular structures in the inferior quadrants of macula are positively correlated with frequency of alcohol use.Also in our study results is that the monthly drinker group has uniquely higher VDs in both macula and OD.This leads us to consider moderate alcohol consumption may also have protective effects on retinal microcirculation.
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 Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
