Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma.Its pathophysiological mechanisms involve primary and secondary injury phases,leading to progressive retinal ganglion cell loss and axonal...Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma.Its pathophysiological mechanisms involve primary and secondary injury phases,leading to progressive retinal ganglion cell loss and axonal degeneration.Contributing factors such as physical trauma,oxidative stress,neuroinflammation,and glial scar formation exacerbate disease progression and retinal ganglion cell death.Multiple forms of cell death—including apoptosis,pyroptosis,necroptosis,and ferroptosis—are involved at different disease stages.Although current treatments,such as corticosteroid therapy and surgical interventions,have limited efficacy,cell-based therapies have emerged as a promising approach that simultaneously promotes neuroprotection and retinal ganglion cell regeneration.This review summarizes recent advances in cell-based therapies for traumatic optic neuropathy.In the context of cell replacement therapy,retinal ganglion cell-like cells derived from embryonic stem cells and induced pluripotent stem cells—via chemical induction or direct reprogramming—have demonstrated the ability to integrate into the host retina and survive for weeks to months,potentially improving visual function.Mesenchymal stem cells derived from various sources,including bone marrow,umbilical cord,placenta,and adipose tissue,have been shown to enhance retinal ganglion cell survival,stimulate axonal regeneration,and support partial functional recovery.Additionally,neural stem/progenitor cells derived from human embryonic stem cells offer neuroprotective effects and function as“neuronal relays,”facilitating reconnection between damaged regions of the optic nerve and the visual pathway.Beyond direct cell transplantation,cell-derived products,such as extracellular vesicles and cell-extracted solutions,have demonstrated promising neuroprotective effects in traumatic optic neuropathy.Despite significant progress,several challenges remain,including limited integration of transplanted cells,suboptimal functional vision recovery,the need for precise timing and delivery methods,and an incomplete understanding of the role of the retinal microenvironment and glial cell activation in neuroprotection and neuroregeneration.Furthermore,studies with longer observation periods and deeper mechanistic insights into the therapeutic effects of cell-based therapies remain scarce.Two Phase I clinical trials have confirmed the safety and potential benefits of cell-based therapy for traumatic optic neuropathy,with reported improvements in visual acuity.However,further studies are needed to validate these findings and establish significant therapeutic outcomes.In conclusion,cell-based therapies hold great promise for treating traumatic optic neuropathy,but critical obstacles must be overcome to achieve functional optic nerve regeneration.Emerging bioengineering strategies,such as scaffold-based transplantation,may improve cell survival and axonal guidance.Successful clinical translation will require rigorous preclinical validation,standardized protocols,and the integration of advanced imaging techniques to optimize therapeutic efficacy.展开更多
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
Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and l...Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and luteolin can independently promote photoreceptor survival and function in degenerated mouse retinas,although with limited efficacy.This study evaluated whether a combination of Lycium barbarum glycopeptide and luteolin provides enhanced therapeutic benefits compared with either compound alone.Wild-type mice received a daily oral gavage of Lycium barbarum glycopeptide and luteolin for 7 days prior to intraperitoneal injection of N-nitroso-N-methylurea to induce photoreceptor damage.The treatment continued for an additional week after injury.Retinal structure and function were subsequently assessed using electroretinogram recordings,visual behavior testing,and immunostaining.Western blot analysis was conducted to investigate the underlying protective mechanisms.The results showed that the Lycium barbarum glycopeptide-luteolin mixture significantly increased photoreceptor survival,improved retinal light response,and enhanced visual behavior.Importantly,the combination outperformed either compound alone in protective efficacy.Mechanistic analysis indicated that the mixture suppressed retinal inflammation and modulated the extracellular signal-regulated kinase and Bcl-2-associated X protein/B-cell lymphoma 2 signaling pathways.These findings suggest that the combination of Lycium barbarum glycopeptide and luteolin represents a promising therapeutic strategy for photoreceptor degeneration.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
At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic reti...At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic retinopathy,hypertension,atherosclerosis and other conditions,with a reported accuracy of about 90 percent.展开更多
Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have fou...Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have found that GHRH possesses functions like antiinflammation,promoting cell proliferation,and facilitating cell migration.It participates in regulating the development of uveitis and diabetic retinopathy.Additionally,it also has an impact on the development of retinal ganglion cells by modulating the inflammatory response and mediating the immune response.Given the important roles of GHRH in ophthalmic diseases,elucidating the molecular regulation of the GHRH-GHRH receptor(GHRHR)signal and the innovative development of intervention pathways that directly or indirectly target GHRH serve as strong evidence of how basic research guides innovation and translation.In this review,research reports on GHRH in ophthalmic diseases including retinal diseases and uveitis were summarized and analyzed.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_(3)F_(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
Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that dem...Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration.Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88.Motivated to study this retinal ganglion cell type,we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential.Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells.Interestingly,we find that ON-direction-selective retinal ganglion cells are resilient,but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments.Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.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
Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility...Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.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
基金supported by the National Key Research and Development Program of China,No.2022YFA1105502(to PG)the National Natural Science Foundation of China,Nos.82271123(to PG),32200618(to ZT)。
文摘Traumatic optic neuropathy is a form of optic neuropathy resulting from trauma.Its pathophysiological mechanisms involve primary and secondary injury phases,leading to progressive retinal ganglion cell loss and axonal degeneration.Contributing factors such as physical trauma,oxidative stress,neuroinflammation,and glial scar formation exacerbate disease progression and retinal ganglion cell death.Multiple forms of cell death—including apoptosis,pyroptosis,necroptosis,and ferroptosis—are involved at different disease stages.Although current treatments,such as corticosteroid therapy and surgical interventions,have limited efficacy,cell-based therapies have emerged as a promising approach that simultaneously promotes neuroprotection and retinal ganglion cell regeneration.This review summarizes recent advances in cell-based therapies for traumatic optic neuropathy.In the context of cell replacement therapy,retinal ganglion cell-like cells derived from embryonic stem cells and induced pluripotent stem cells—via chemical induction or direct reprogramming—have demonstrated the ability to integrate into the host retina and survive for weeks to months,potentially improving visual function.Mesenchymal stem cells derived from various sources,including bone marrow,umbilical cord,placenta,and adipose tissue,have been shown to enhance retinal ganglion cell survival,stimulate axonal regeneration,and support partial functional recovery.Additionally,neural stem/progenitor cells derived from human embryonic stem cells offer neuroprotective effects and function as“neuronal relays,”facilitating reconnection between damaged regions of the optic nerve and the visual pathway.Beyond direct cell transplantation,cell-derived products,such as extracellular vesicles and cell-extracted solutions,have demonstrated promising neuroprotective effects in traumatic optic neuropathy.Despite significant progress,several challenges remain,including limited integration of transplanted cells,suboptimal functional vision recovery,the need for precise timing and delivery methods,and an incomplete understanding of the role of the retinal microenvironment and glial cell activation in neuroprotection and neuroregeneration.Furthermore,studies with longer observation periods and deeper mechanistic insights into the therapeutic effects of cell-based therapies remain scarce.Two Phase I clinical trials have confirmed the safety and potential benefits of cell-based therapy for traumatic optic neuropathy,with reported improvements in visual acuity.However,further studies are needed to validate these findings and establish significant therapeutic outcomes.In conclusion,cell-based therapies hold great promise for treating traumatic optic neuropathy,but critical obstacles must be overcome to achieve functional optic nerve regeneration.Emerging bioengineering strategies,such as scaffold-based transplantation,may improve cell survival and axonal guidance.Successful clinical translation will require rigorous preclinical validation,standardized protocols,and the integration of advanced imaging techniques to optimize therapeutic efficacy.
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Natural Science Foundation of Guangdong Province,No.2023A1515012397(to YX)the National Natural Science Foundation of China,No.82074169(to XM)+2 种基金the Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012473(to XM)and Project of Administration of Traditional Chinese Medicine of Guangdong Province,No.20202045(to XM)Aier Eye Hospital Group,No.AF2019001(to ST,KFS,YX,and XM).
文摘Photoreceptor degeneration is a major cause of vision impairment in retinal diseases,for which no effective treatment currently exists.Previous research by our team demonstrated that Lycium barbarum glycopeptide and luteolin can independently promote photoreceptor survival and function in degenerated mouse retinas,although with limited efficacy.This study evaluated whether a combination of Lycium barbarum glycopeptide and luteolin provides enhanced therapeutic benefits compared with either compound alone.Wild-type mice received a daily oral gavage of Lycium barbarum glycopeptide and luteolin for 7 days prior to intraperitoneal injection of N-nitroso-N-methylurea to induce photoreceptor damage.The treatment continued for an additional week after injury.Retinal structure and function were subsequently assessed using electroretinogram recordings,visual behavior testing,and immunostaining.Western blot analysis was conducted to investigate the underlying protective mechanisms.The results showed that the Lycium barbarum glycopeptide-luteolin mixture significantly increased photoreceptor survival,improved retinal light response,and enhanced visual behavior.Importantly,the combination outperformed either compound alone in protective efficacy.Mechanistic analysis indicated that the mixture suppressed retinal inflammation and modulated the extracellular signal-regulated kinase and Bcl-2-associated X protein/B-cell lymphoma 2 signaling pathways.These findings suggest that the combination of Lycium barbarum glycopeptide and luteolin represents a promising therapeutic strategy for photoreceptor degeneration.
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.
文摘At Beijing Tongren Hospital,an AI-powered retinal screening system can screen for 10 chronic illnesses from just two photos in two minutes.Using one fundus image from each eye,it scans for early signs of diabetic retinopathy,hypertension,atherosclerosis and other conditions,with a reported accuracy of about 90 percent.
基金Supported by Central Government Guidance Funds for Local Science and Technology Development 2024(No.STKJ2024074).
文摘Growth hormone-releasing hormone(GHRH)is a hypothalamic releasing hormone that plays a crucial physiological role in regulating the synthesis and release of anterior pituitary hormones.In recent years,studies have found that GHRH possesses functions like antiinflammation,promoting cell proliferation,and facilitating cell migration.It participates in regulating the development of uveitis and diabetic retinopathy.Additionally,it also has an impact on the development of retinal ganglion cells by modulating the inflammatory response and mediating the immune response.Given the important roles of GHRH in ophthalmic diseases,elucidating the molecular regulation of the GHRH-GHRH receptor(GHRHR)signal and the innovative development of intervention pathways that directly or indirectly target GHRH serve as strong evidence of how basic research guides innovation and translation.In this review,research reports on GHRH in ophthalmic diseases including retinal diseases and uveitis were summarized and analyzed.
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_(3)F_(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Institutional National Research Service Award T32 EY013360(to SM and SW)Research to Prevent Blindness(Career Development Award+8 种基金to PRW)BrightFocus Foundation(National Glaucoma Researchto PRW)Alcon Research Institute(Young Investigator Awardto PRW),and NIH Grants(EY032908,EY035684,EY036111to PRW)the Jefferey T.Fort Innovation Fund and Siteman Retina Research Fund(to RSA)the Hope Center Viral Vectors Core at Washington University School of Medicine,an unrestricted grant(to the Department of Ophthalmology and Visual Sciences)from Research to Prevent BlindnessVision Core Grant(P30 EY002687).
文摘Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration.Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88.Motivated to study this retinal ganglion cell type,we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential.Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells.Interestingly,we find that ON-direction-selective retinal ganglion cells are resilient,but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments.Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.
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(62522119 and 62372358)the Beijing Natural Science Foundation(7242267)+2 种基金the Beijing Scholars Program([2015]160)the Natural Science Basic Research Program of Shaanxi(2023-JC-QN-0719)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110453)。
文摘Background:Brain volume measurement serves as a critical approach for assessing brain health status.Considering the close biological connection between the eyes and brain,this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata,and to offer a cost-effective approach for assessing brain health.Methods:Based on clinical information,retinal fundus images,and neuroimaging data derived from a multicenter,population-based cohort study,the Kai Luan Study,we proposed a cross-modal correlation representation(CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects.Specifically,individual clinical information,which has been followed up for as long as 12 years,was encoded as a prompt to enhance the accuracy of brain volume estimation.Independent internal validation and external validation were performed to assess the robustness of the proposed model.Root mean square error(RMSE),peak signal-tonoise ratio(PSNR),and structural similarity index measure(SSIM)metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.Results:The proposed framework yielded average RMSE,PSNR,and SSIM values of 98.23,35.78 d B,and 0.64,respectively,which significantly outperformed 5 other methods:multi-channel Variational Autoencoder(mcVAE),Pixelto-Pixel(Pixel2pixel),transformer-based U-Net(Trans UNet),multi-scale transformer network(MT-Net),and residual vision transformer(ResViT).The two-(2D)and three-dimensional(3D)visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images.Thus,the CMCR framework accurately captured the latent structural correlations between the fundus and the brain.The average difference between predicted and actual brain volumes was 61.36 cm~3,with a relative error of 4.54%.When all of the clinical information(including age and sex,daily habits,cardiovascular factors,metabolic factors,and inflammatory factors)was encoded,the difference was decreased to 53.89 cm~3,with a relative error of 3.98%.Based on the synthesized brain magnetic resonance images from retinal fundus images,the volumes of brain tissues could be estimated with high accuracy.Conclusion:This study provides an innovative,accurate,and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.
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.
