AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This...AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.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
Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic ...Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.展开更多
Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundu...Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundus fluorescein angiography(FFA)and optical coherence tomography(OCT),which show delayed retinal artery filling time hours to days after occlusion and increased hyperreflectivity of the inner retina.展开更多
AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to s...AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to simulate the retinal ischemia.All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development.Paraffin section staining was used for detecting changes in organoid structure and cell number.Real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot(WB)analyses were used to observe the change in the expression of retinal cell markers.RESULTS:In hROs,OGD/R induced the decrease of proliferating cells,inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells(P<0.05).Under OGD/R condition,the progenitor cell layer and ganglion cell layer of hROs lost normal structure,and the number of neural stem cells(SOX2^(+)),retinal progenitor cells(CHX10^(+))and retinal ganglion cells(TUJ1^(+)/BRN3^(+)/ATOH7^(+))decreased(P<0.05).The expression of corresponding retinal cell markers also decreased(P<0.05).Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18.Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60,with no recovery in proliferating cell nuclear antigen(PCNA)protein expression.RT-qPCR showed persistently low Ki67 transcription levels(P<0.001),while other retinal cell markers recovered or exceeded normal levels,indicating a limited self-repair happened in the development of hROs.In contrast,day 30-treated organoids exhibited normal structure and marker expression by day 60,with transcription levels of retinal cell markers returning to normal(P>0.05),demonstrating complete recovery from OGD/R damage.CONCLUSION:Retinal ischemia damage the retinal development in the short-term.After the restoration of retinal blood supply,the retinal ischemic damage can be recovered during subsequent development.However,retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility.The earlier ischemic injury occurs,the more difficult it is to repair retinal cell and structure damage.展开更多
AIM:To evaluate alterations in conjunctival vascular density(CVD)and macular capillary density(MCD)in female patients with type 2 diabetes mellitus(T2DM)and gestational diabetes mellitus(GDM)using optical coherence to...AIM:To evaluate alterations in conjunctival vascular density(CVD)and macular capillary density(MCD)in female patients with type 2 diabetes mellitus(T2DM)and gestational diabetes mellitus(GDM)using optical coherence tomography angiography(OCTA).METHODS:A total of 60 female participants were recruited,comprising 20 patients with T2DM,20 patients with GDM,and 20 healthy age-matched controls(HCs).OCTA was used to assess superficial and deep retinal and conjunctival capillary plexuses.Subsequently,changes in MCD were analyzed using a circular segmentation method(C1-C6),a hemispheric quadrant segmentation method[superior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and the early treatment diabetic retinopathy study(ETDRS)segmentation method(S,I,R,L).RESULTS:OCTA unequivocally demonstrated that the variations in CVD among HCs,T2DM,and GDM groups were statistically significant(P<0.001).In the superficial retinal capillary plexus(sRCP),significant differences were observed in the densities of total microvascular(TMI),microvasculature(MIR),and macrovascular(MAR)between patients with T2DM and HCs(P<0.05).Furthermore,the GDM group exhibited a more substantial reduction in MIR density compared to the T2DM group(P<0.01).In the deep retinal capillary plexus(dRCP),significant differences in the densities of TMI and MIR were identified between the T2DM group and HCs(P<0.05),with a notable difference in TMI density also observed between the GDM and T2DM groups(P<0.01).In the receiver operating characteristic(ROC)curve analysis,the area under the ROC curve(AUC)for TMI in sRCP between the T2DM group and HCs was 0.975,with a 95%confidence interval(CI)of 0.941–1.The AUC for MIR was highest in dRCP,with an AUC value of 0.914 and a 95%CI ranging from 0.847 to 0.981.In comparing the GDM and T2DM groups,the AUC for I region was maximized in sRCP,achieving a value of 0.978 with a 95%CI of 0.953–1.Additionally,the AUC for R region was maximized in dRCP,reaching a value of 0.99 with a 95%CI of 0.975 to 1.CONCLUSION:The sRCP and dRCP densities show higher diagnostic sensitivity for T2DM and GDM.OCTA holds potential as a significant instrument for the early diagnosis and differentiation of T2DM and GDM.展开更多
A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and contin...The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.展开更多
Improvements in surgical techniques have led to 90% success in the surgical repair of rhegmatogenous retinal detachment(RRD).However,anatomical reattachment of the retina does not ensure complete recovery of visual fu...Improvements in surgical techniques have led to 90% success in the surgical repair of rhegmatogenous retinal detachment(RRD).However,anatomical reattachment of the retina does not ensure complete recovery of visual function.The incidence of metamorphopsia remains the most common postoperative complaint,from 24% to 88.6%.Currently,the risk factors of metamorphopsia are categorized into macular involvement,retinal shift,outer retinal folds,subretinal fluid,secondary epiretinal membrane,outer retinal layer damage,and surgical approach.The associations of metamorphopsia with postoperative best-corrected visual acuity and postoperative vision-related quality of life were still controversial.The most popular methods for assessment of metamorphopsia remain the Amsler grid and M-Charts.Most treatments cannot progress beyond the management of negative visual sensations,through methods such as occlusion therapy and aniseikonia-correcting spectacles.The main treatment approach involves RRD prevention and the management of risk factors that can lead to postoperative metamorphopsia after RRD repair.Additional research concerning metamorphopsia treatment,further upgrades of auxiliary inspection methods,and more accurate microstructural assessments are needed to address this common complication.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
AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured R...AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.展开更多
Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to ...Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.展开更多
1 Introduction Retinal vessel analysis plays a crucial role in the detection and management of various systemic and ocular diseases,such as diabetic retinopathy,hypertension and cardiovascular disorders[1].Precise seg...1 Introduction Retinal vessel analysis plays a crucial role in the detection and management of various systemic and ocular diseases,such as diabetic retinopathy,hypertension and cardiovascular disorders[1].Precise segmentation of retinal vessels from fundus images enables clinicians to analyze vessel morphology,which can reveal disease progression or underlying conditions.Over recent years,deep learning methods have significantly advanced retinal vessel segmentation.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
AIM:To report the refractive and surgical outcomes of scleral buckling(SB)with or without pars plana vitrectomy(PPV)in patients with pseudophakic rhegmatogenous retinal detachment(PRRD).METHODS:A consecutive case seri...AIM:To report the refractive and surgical outcomes of scleral buckling(SB)with or without pars plana vitrectomy(PPV)in patients with pseudophakic rhegmatogenous retinal detachment(PRRD).METHODS:A consecutive case series of patients with pseudophakia who underwent retinal detachment(RD)surgery was enrolled.The SB procedures were selected to initially treat primary pseudophakic PRRDs and SB-PPV for more complex cases,according to preoperative findings.Eyes with anterior chamber intraocular lens,proliferative vitreoretinopathy anterior to equator,previous invasive glaucoma surgery,severe degenerative myopia or macular hole,and<6mo follow-up were excluded from outcomes analysis.The primary clinical outcome measures were the single surgery anatomic success(SSAS)and final surgery anatomic success(FSAS)rates.Secondary outcome measures were postoperative visual acuity and refractive error.RESULTS:A total of 81 consecutive patients(81 eyes)were enrolled for analysis,comprising 66(81%)men and 15(19%)women with a mean age of 58y(range,33-86y)and the mean final follow-up period was 21.0±19.6mo.A total of 62 PRRDs(n=62;76.5%)were repaired with an initial SB,and 19 PRRDs(n=19;23.5%)were repaired with a combined SB-PPV.The SSAS and FSAS rates were 92.6%(75/81)and 100%(81/81),respectively.All initial failures had retinal reattachment after the secondary PPV.The mean final postoperative best-corrected visual acuity(BCVA)was 0.42±0.33 logMAR(visual acuity 20/55)and final mean refractive error was-1.48±1.40 diopters.The patients who underwent initially SB-PPV had a significantly longer duration of RD and a higher giant retinal tear rate(P<0.05)preoperatively.SSAS was 56/62(90.3%)and 19/19(100%),and the mean postoperative refractive error was-1.30±1.32 D and-1.53±1.38 D for the patients in the SB and SB-PPV groups,respectively.There was no statistically significant difference for those who had SSAS and postoperative refractive errors between the 2 groups.The postoperative BCVAs of the patients with SSAS were not significantly better in the SB group(median,20/40)than in the SB-PPV group(median 20/50).In the SB group,patients with macula-on had better visual acuity postoperatively than patients with macula-off(P=0.000).CONCLUSION:The initial surgical procedures of SB with or without PPV according to the preoperative findings achieve a high reattachment rate and an acceptable refractive error for primary pseudophakic RRD management.展开更多
Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current...Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current clinical strategies are limited.This study aimed to elucidate how electroacupuncture(EA)protects the OBRB against RIR injury.Methods Male Wistar rats(7 weeks old,250 g to 280 g)were used in this study.Three independent experiments were conducted.First,Opioid peptide levels were quantified using enzyme-linked immunosorbent assay(ELISA).42 rats were randomly divided into 7 groups(n=6/group):Control:No treatment;high intraocular pressure(HIOP):Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming(Extra acupoint)and Jingming(BL1)for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;HIOP+100 Hz:RIR injury+100 Hz EA at Xinming and BL1 for 30 min;HIOP+2/100 Hz EA:RIR injury+2/100 Hz EA at Xinming and BL1 for 30 min;HIOP+4/20 Hz EA:RIR injury+4/20 Hz EA at Xinming and BL1 for 30 min.Second,retinal morphology was assessed by hematoxylin and eosin(HE)staining.20 rats were randomly allocated into 4 groups(n=5/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min.Third,the permeability of OBRB was evaluated using the fluorescein isothiocyanate(FITC)-dextran leakage assay.15 rats were randomly divided into 5 groups(n=3/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;Nal+HIOP+2 Hz EA:Intravitreal injection ofδ-opioid receptor antagonist Naltridole(10µl,100 nM)30 min before RIR injury induction,followed by 2 Hz EA treatment at Xinming and BL1 for 30 min.In vitro studies examined enkephalins'effects on oxygen–glucose deprivation/reperfusion(OGD/R)induced injury in ARPE‐19 cells.Cell viability was evaluated by cell counting kit-8(CCK-8)assay,and morphological changes were recorded by Molecular Devices.Apoptosis was detected by Annexin V-FITC flow cytometry.Delta opioid receptor(DOR)expression in total protein and membrane protein were analyzed by western blotting(WB).Immunofluorescence(IF)staining and WB assessed ZO-1 and Claudin-19.For cell-based assays,n indicates the number of biologically independent replicates.Results It was found that 2 Hz EA treatment increased enkephalins(methionine-enkephalin and leucine-enkephalin)levels(P<0.01),restoring the increased retinal thickness(P<0.05)and mitigating RGCs loss(P<0.05)post-RIR injury.FITC-dextran leakage in the outer retina was ameliorated by 2 Hz EA(P<0.05),reversibly countered by Naltrindole(P<0.05),a DOR antagonist.Treatment with 30µM enkephalins enhanced ARPE-19 cell viability(P<0.001,P<0.0001)and inhibited apoptosis(P<0.0001).Enkephalins elevated DOR levels in total protein(P<0.05)and membrane protein fractions(P<0.001,P<0.0001),as well as elevated ZO-1(P<0.001,P<0.01)and Claudin-19(P<0.0001,P<0.001)levels following OGD/R,counteracted by Naltrindole.Conclusion It was found that 2 Hz EA inhibits the breakdown of OBRB via enkephalins activate DOR in RIR injury.展开更多
Retinal pigment epithelium(RPE)dysfunction is involved in the advancement of numerous degenerative retinal illnesses,such as age-related macular degeneration and hereditary retinal abnormalities.Transplantation of RPE...Retinal pigment epithelium(RPE)dysfunction is involved in the advancement of numerous degenerative retinal illnesses,such as age-related macular degeneration and hereditary retinal abnormalities.Transplantation of RPE produced from stem cells has emerged as a promising therapeutic strategy to restore retinal function and prevent vision loss.However,other obstacles impede its clinical application,including immunological rejection,cell viability,functional integration,and the necessity for consistent differentiation techniques.This review offers a thorough examination of the molecular processes regulating RPE integrity,investigates recent progress in stem cell-derived RPE therapeutics,and addresses significant challenges to their broad implementation.Furthermore,we emphasize prospective avenues intended to enhance the safety,efficacy,and enduring success of RPE transplantation in clinical environments.展开更多
AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were i...AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were isolated from optic cups of rats on embryonic day 12.5,and high-purity OC-RSCs were obtained by conditioned culture and passage.Differentiation of OC-RSCs into RGCs under different serum concentrations was examined using flow cytometry,and the serum concentration with high interference with differentiation ratio was selected.Furthermore,the effect of blocking IGF-1Rαon the differentiation of OC-RSCs into RGCs was analyzed through immunocytochemistry and Western blotting.RESULTS:Immunohistochemical analysis revealed IGF-1Rαwas highly expressed in rat embryos at day 12.5.OC-RSCs were isolated and purified,and high-purity OCRSCs were obtained.When 2.5%serum was administered,the ratio of differentiated RGCs(Thy-1.1 positive)decreased significantly,and the results of immunoblotting also confirmed the blockade of IGF-1Rαreduced Thy-1.1 protein expression.CONCLUSION:IGF-1Rαblocking can reduce the differentiation of OC-RSCs into RGCs.展开更多
AIM:To compare the proportion of rhegmatogenous retinal detachment(RRD)associated with choroidal detachment(RRDCD)in the emergency surgery group with the routine inpatient surgery group and determine risk factors for ...AIM:To compare the proportion of rhegmatogenous retinal detachment(RRD)associated with choroidal detachment(RRDCD)in the emergency surgery group with the routine inpatient surgery group and determine risk factors for RRDCD.METHODS:A total of 694 patients(694 eyes)diagnosed with RRD in the emergency surgery(the median duration of RRD was 5d)group were included from the Department of Ophthalmic Emergency,and 692 patients(eyes)in the routine inpatient surgery group(the median duration was 15d)were selected randomly from the Ocular Fundus Department.Demographics,refractive status,macular status,lens status,extent of retinal detachment,number of retinal breaks,duration of symptoms before surgery,and the incidence of RRDCD were compared.A logistic regression analysis was used to determine potential risk factors for RRDCD.RESULTS:Compared to the routine inpatient surgery group,the emergency surgery group had a significant less median time to surgery(P<0.001)and a decreased proportion of RRDCD(2.88%vs 10.84%,P<0.001).Logistic regression analysis revealed that a prolonged duration of RRD[OR 3.51,95%confidence interval(CI)1.98-6.23],pseudophakia/aphakia status[OR 2.74,95%CI(1.50-4.98)],multiple retinal breaks[OR 1.67,95%CI(1.03-2.70)],and a substantial extent of RRD[OR 11.58,95%CI(7.12-18.84)]were independent risk factors for RRDCD.CONCLUSION:Emergency surgical pattern of RRD demonstrates a lower incidence of RRDCD.The adoption of an expedited surgical approach has the potential to reduce the duration of RRD,possibly correlating with a decreased risk of RRDCD development.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
基金Supported by the Suzhou Medical Innovation Application Research Project(SZM2023027).
文摘AIM:To explore the morphological and functional parameters to evaluate the effectiveness of intravitreal injections of ranibizumab(IVR)in treating macular edema(ME)secondary to retinal vein occlusion(RVO).METHODS:This retrospective study involved 65 RVO patients(65 eyes)who received IVR and were followedup for more than 3mo.ME was categorized into cystoid macular edema(CME),diffuse retinal thickening(DRT),and serous retinal detachment(SRD)according to optical coherence tomography(OCT)images.The comparison of best corrected visual acuity(BCVA;logMAR)and central macular thickness(CMT)among different follow-up points and those among 3 groups were performed by Kruskal-Wallis test.The correlation between BCVA and baseline parameters during treatment was analyzed using Spearman correlation analysis.RESULTS:BCVA tended to improve in all groups,with marked improvement in CME and DRT groups.CMT showed the greatest reduction after 1wk,and remained stable over the following 3mo.DRT patients had the worst BCVA and the highest CMT at baseline,but the differences became smaller after IVR treatment.CMT in SRD group was significantly better than in CME and DRT groups 3mo after IVR.Most patients of CME and SRD groups transitioned to a normal pattern at 3mo follow-up.DRT patients were most likely to transform into the other morphological groups,while SRD patients showed minimal transitions.BCVA at baseline was identified as the most important prognostic indicator in all 3 groups.Additionally,DRT patients with a longer clinical course,higher CMT and central retinal vein occlusion(CRVO)tend to exhibit worse BCVA after treatment.In addition,CRVO patients are more likely to have worse BCVA at 2 and 3mo follow-up compared with branch retinal vein occlusion(BRVO)patients in CME group.SRD patients with higher baseline CMT were prone to experiencing worse BCVA after treatment.CONCLUSION:The effectiveness of IVR is strongly correlated with baseline BCVA in all 3 groups.Baseline parameters including clinical course,CMT,and RVO position are also useful in predicting the BCVA at different time points after treatment.
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.
文摘Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.
基金Supported by National Natural Science Foundation of China(No.82070991).
文摘Central retinal artery occlusion(CRAO)is an acute ophthalmic emergency,characterized by sudden vision loss due to retinal ischemia in areas corresponding to arterial occlusion sites.Diagnosis primarily relies on fundus fluorescein angiography(FFA)and optical coherence tomography(OCT),which show delayed retinal artery filling time hours to days after occlusion and increased hyperreflectivity of the inner retina.
基金Supported by the National Natural Science Foundation of China(No.82070937).
文摘AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to simulate the retinal ischemia.All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development.Paraffin section staining was used for detecting changes in organoid structure and cell number.Real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot(WB)analyses were used to observe the change in the expression of retinal cell markers.RESULTS:In hROs,OGD/R induced the decrease of proliferating cells,inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells(P<0.05).Under OGD/R condition,the progenitor cell layer and ganglion cell layer of hROs lost normal structure,and the number of neural stem cells(SOX2^(+)),retinal progenitor cells(CHX10^(+))and retinal ganglion cells(TUJ1^(+)/BRN3^(+)/ATOH7^(+))decreased(P<0.05).The expression of corresponding retinal cell markers also decreased(P<0.05).Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18.Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60,with no recovery in proliferating cell nuclear antigen(PCNA)protein expression.RT-qPCR showed persistently low Ki67 transcription levels(P<0.001),while other retinal cell markers recovered or exceeded normal levels,indicating a limited self-repair happened in the development of hROs.In contrast,day 30-treated organoids exhibited normal structure and marker expression by day 60,with transcription levels of retinal cell markers returning to normal(P>0.05),demonstrating complete recovery from OGD/R damage.CONCLUSION:Retinal ischemia damage the retinal development in the short-term.After the restoration of retinal blood supply,the retinal ischemic damage can be recovered during subsequent development.However,retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility.The earlier ischemic injury occurs,the more difficult it is to repair retinal cell and structure damage.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)The Science and Technology Innovation Program of Changde City(No.2023YD25).
文摘AIM:To evaluate alterations in conjunctival vascular density(CVD)and macular capillary density(MCD)in female patients with type 2 diabetes mellitus(T2DM)and gestational diabetes mellitus(GDM)using optical coherence tomography angiography(OCTA).METHODS:A total of 60 female participants were recruited,comprising 20 patients with T2DM,20 patients with GDM,and 20 healthy age-matched controls(HCs).OCTA was used to assess superficial and deep retinal and conjunctival capillary plexuses.Subsequently,changes in MCD were analyzed using a circular segmentation method(C1-C6),a hemispheric quadrant segmentation method[superior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and the early treatment diabetic retinopathy study(ETDRS)segmentation method(S,I,R,L).RESULTS:OCTA unequivocally demonstrated that the variations in CVD among HCs,T2DM,and GDM groups were statistically significant(P<0.001).In the superficial retinal capillary plexus(sRCP),significant differences were observed in the densities of total microvascular(TMI),microvasculature(MIR),and macrovascular(MAR)between patients with T2DM and HCs(P<0.05).Furthermore,the GDM group exhibited a more substantial reduction in MIR density compared to the T2DM group(P<0.01).In the deep retinal capillary plexus(dRCP),significant differences in the densities of TMI and MIR were identified between the T2DM group and HCs(P<0.05),with a notable difference in TMI density also observed between the GDM and T2DM groups(P<0.01).In the receiver operating characteristic(ROC)curve analysis,the area under the ROC curve(AUC)for TMI in sRCP between the T2DM group and HCs was 0.975,with a 95%confidence interval(CI)of 0.941–1.The AUC for MIR was highest in dRCP,with an AUC value of 0.914 and a 95%CI ranging from 0.847 to 0.981.In comparing the GDM and T2DM groups,the AUC for I region was maximized in sRCP,achieving a value of 0.978 with a 95%CI of 0.953–1.Additionally,the AUC for R region was maximized in dRCP,reaching a value of 0.99 with a 95%CI of 0.975 to 1.CONCLUSION:The sRCP and dRCP densities show higher diagnostic sensitivity for T2DM and GDM.OCTA holds potential as a significant instrument for the early diagnosis and differentiation of T2DM and GDM.
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
文摘Improvements in surgical techniques have led to 90% success in the surgical repair of rhegmatogenous retinal detachment(RRD).However,anatomical reattachment of the retina does not ensure complete recovery of visual function.The incidence of metamorphopsia remains the most common postoperative complaint,from 24% to 88.6%.Currently,the risk factors of metamorphopsia are categorized into macular involvement,retinal shift,outer retinal folds,subretinal fluid,secondary epiretinal membrane,outer retinal layer damage,and surgical approach.The associations of metamorphopsia with postoperative best-corrected visual acuity and postoperative vision-related quality of life were still controversial.The most popular methods for assessment of metamorphopsia remain the Amsler grid and M-Charts.Most treatments cannot progress beyond the management of negative visual sensations,through methods such as occlusion therapy and aniseikonia-correcting spectacles.The main treatment approach involves RRD prevention and the management of risk factors that can lead to postoperative metamorphopsia after RRD repair.Additional research concerning metamorphopsia treatment,further upgrades of auxiliary inspection methods,and more accurate microstructural assessments are needed to address this common complication.
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 Science and Technology Research Project of Hubei Provincial Department of Education(No.B2021108).
文摘AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.
基金supported by grants from National Natural Science Foundation of China(81720108012,82001118)Ministry of Science and Technology of China(2021ZD0202003)+1 种基金Shanghai‘Rising Stars of Medical Talents’Youth Development Program(SHWSRS(2023)-62)Henry K.Beecher Professorship from Harvard University。
文摘Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.
基金supported by the Shuangchuang Ph.D award,Jiangsu,China(No.JSSCBS20210804)the National Natural Science Foundation of China(Grant No.62201460)the Basic Research Programs of Taicang(No.TC2023JC22).
文摘1 Introduction Retinal vessel analysis plays a crucial role in the detection and management of various systemic and ocular diseases,such as diabetic retinopathy,hypertension and cardiovascular disorders[1].Precise segmentation of retinal vessels from fundus images enables clinicians to analyze vessel morphology,which can reveal disease progression or underlying conditions.Over recent years,deep learning methods have significantly advanced retinal vessel segmentation.
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).
文摘AIM:To report the refractive and surgical outcomes of scleral buckling(SB)with or without pars plana vitrectomy(PPV)in patients with pseudophakic rhegmatogenous retinal detachment(PRRD).METHODS:A consecutive case series of patients with pseudophakia who underwent retinal detachment(RD)surgery was enrolled.The SB procedures were selected to initially treat primary pseudophakic PRRDs and SB-PPV for more complex cases,according to preoperative findings.Eyes with anterior chamber intraocular lens,proliferative vitreoretinopathy anterior to equator,previous invasive glaucoma surgery,severe degenerative myopia or macular hole,and<6mo follow-up were excluded from outcomes analysis.The primary clinical outcome measures were the single surgery anatomic success(SSAS)and final surgery anatomic success(FSAS)rates.Secondary outcome measures were postoperative visual acuity and refractive error.RESULTS:A total of 81 consecutive patients(81 eyes)were enrolled for analysis,comprising 66(81%)men and 15(19%)women with a mean age of 58y(range,33-86y)and the mean final follow-up period was 21.0±19.6mo.A total of 62 PRRDs(n=62;76.5%)were repaired with an initial SB,and 19 PRRDs(n=19;23.5%)were repaired with a combined SB-PPV.The SSAS and FSAS rates were 92.6%(75/81)and 100%(81/81),respectively.All initial failures had retinal reattachment after the secondary PPV.The mean final postoperative best-corrected visual acuity(BCVA)was 0.42±0.33 logMAR(visual acuity 20/55)and final mean refractive error was-1.48±1.40 diopters.The patients who underwent initially SB-PPV had a significantly longer duration of RD and a higher giant retinal tear rate(P<0.05)preoperatively.SSAS was 56/62(90.3%)and 19/19(100%),and the mean postoperative refractive error was-1.30±1.32 D and-1.53±1.38 D for the patients in the SB and SB-PPV groups,respectively.There was no statistically significant difference for those who had SSAS and postoperative refractive errors between the 2 groups.The postoperative BCVAs of the patients with SSAS were not significantly better in the SB group(median,20/40)than in the SB-PPV group(median 20/50).In the SB group,patients with macula-on had better visual acuity postoperatively than patients with macula-off(P=0.000).CONCLUSION:The initial surgical procedures of SB with or without PPV according to the preoperative findings achieve a high reattachment rate and an acceptable refractive error for primary pseudophakic RRD management.
基金Supported by the National Natural Science Foundation of China:81574078。
文摘Objectives Retinal ischemia-reperfusion(RIR)injury results in irreversible visual impairments.The disruption of the outer blood-retinal barrier(OBRB)is a major ocular pathogenic process that RIR injury affects.Current clinical strategies are limited.This study aimed to elucidate how electroacupuncture(EA)protects the OBRB against RIR injury.Methods Male Wistar rats(7 weeks old,250 g to 280 g)were used in this study.Three independent experiments were conducted.First,Opioid peptide levels were quantified using enzyme-linked immunosorbent assay(ELISA).42 rats were randomly divided into 7 groups(n=6/group):Control:No treatment;high intraocular pressure(HIOP):Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming(Extra acupoint)and Jingming(BL1)for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;HIOP+100 Hz:RIR injury+100 Hz EA at Xinming and BL1 for 30 min;HIOP+2/100 Hz EA:RIR injury+2/100 Hz EA at Xinming and BL1 for 30 min;HIOP+4/20 Hz EA:RIR injury+4/20 Hz EA at Xinming and BL1 for 30 min.Second,retinal morphology was assessed by hematoxylin and eosin(HE)staining.20 rats were randomly allocated into 4 groups(n=5/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min.Third,the permeability of OBRB was evaluated using the fluorescein isothiocyanate(FITC)-dextran leakage assay.15 rats were randomly divided into 5 groups(n=3/group):Control:No treatment;HIOP:Acute intraocular pressure elevation-induced RIR injury;HIOP+SHAM EA:RIR injury+sham EA at Xinming and BL1 for 30 min(shallow needle insertion but without electric stimulation);HIOP+2 Hz EA:RIR injury+2 Hz EA at Xinming and BL1 for 30 min;Nal+HIOP+2 Hz EA:Intravitreal injection ofδ-opioid receptor antagonist Naltridole(10µl,100 nM)30 min before RIR injury induction,followed by 2 Hz EA treatment at Xinming and BL1 for 30 min.In vitro studies examined enkephalins'effects on oxygen–glucose deprivation/reperfusion(OGD/R)induced injury in ARPE‐19 cells.Cell viability was evaluated by cell counting kit-8(CCK-8)assay,and morphological changes were recorded by Molecular Devices.Apoptosis was detected by Annexin V-FITC flow cytometry.Delta opioid receptor(DOR)expression in total protein and membrane protein were analyzed by western blotting(WB).Immunofluorescence(IF)staining and WB assessed ZO-1 and Claudin-19.For cell-based assays,n indicates the number of biologically independent replicates.Results It was found that 2 Hz EA treatment increased enkephalins(methionine-enkephalin and leucine-enkephalin)levels(P<0.01),restoring the increased retinal thickness(P<0.05)and mitigating RGCs loss(P<0.05)post-RIR injury.FITC-dextran leakage in the outer retina was ameliorated by 2 Hz EA(P<0.05),reversibly countered by Naltrindole(P<0.05),a DOR antagonist.Treatment with 30µM enkephalins enhanced ARPE-19 cell viability(P<0.001,P<0.0001)and inhibited apoptosis(P<0.0001).Enkephalins elevated DOR levels in total protein(P<0.05)and membrane protein fractions(P<0.001,P<0.0001),as well as elevated ZO-1(P<0.001,P<0.01)and Claudin-19(P<0.0001,P<0.001)levels following OGD/R,counteracted by Naltrindole.Conclusion It was found that 2 Hz EA inhibits the breakdown of OBRB via enkephalins activate DOR in RIR injury.
文摘Retinal pigment epithelium(RPE)dysfunction is involved in the advancement of numerous degenerative retinal illnesses,such as age-related macular degeneration and hereditary retinal abnormalities.Transplantation of RPE produced from stem cells has emerged as a promising therapeutic strategy to restore retinal function and prevent vision loss.However,other obstacles impede its clinical application,including immunological rejection,cell viability,functional integration,and the necessity for consistent differentiation techniques.This review offers a thorough examination of the molecular processes regulating RPE integrity,investigates recent progress in stem cell-derived RPE therapeutics,and addresses significant challenges to their broad implementation.Furthermore,we emphasize prospective avenues intended to enhance the safety,efficacy,and enduring success of RPE transplantation in clinical environments.
文摘AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were isolated from optic cups of rats on embryonic day 12.5,and high-purity OC-RSCs were obtained by conditioned culture and passage.Differentiation of OC-RSCs into RGCs under different serum concentrations was examined using flow cytometry,and the serum concentration with high interference with differentiation ratio was selected.Furthermore,the effect of blocking IGF-1Rαon the differentiation of OC-RSCs into RGCs was analyzed through immunocytochemistry and Western blotting.RESULTS:Immunohistochemical analysis revealed IGF-1Rαwas highly expressed in rat embryos at day 12.5.OC-RSCs were isolated and purified,and high-purity OCRSCs were obtained.When 2.5%serum was administered,the ratio of differentiated RGCs(Thy-1.1 positive)decreased significantly,and the results of immunoblotting also confirmed the blockade of IGF-1Rαreduced Thy-1.1 protein expression.CONCLUSION:IGF-1Rαblocking can reduce the differentiation of OC-RSCs into RGCs.
基金Supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.C2022060).
文摘AIM:To compare the proportion of rhegmatogenous retinal detachment(RRD)associated with choroidal detachment(RRDCD)in the emergency surgery group with the routine inpatient surgery group and determine risk factors for RRDCD.METHODS:A total of 694 patients(694 eyes)diagnosed with RRD in the emergency surgery(the median duration of RRD was 5d)group were included from the Department of Ophthalmic Emergency,and 692 patients(eyes)in the routine inpatient surgery group(the median duration was 15d)were selected randomly from the Ocular Fundus Department.Demographics,refractive status,macular status,lens status,extent of retinal detachment,number of retinal breaks,duration of symptoms before surgery,and the incidence of RRDCD were compared.A logistic regression analysis was used to determine potential risk factors for RRDCD.RESULTS:Compared to the routine inpatient surgery group,the emergency surgery group had a significant less median time to surgery(P<0.001)and a decreased proportion of RRDCD(2.88%vs 10.84%,P<0.001).Logistic regression analysis revealed that a prolonged duration of RRD[OR 3.51,95%confidence interval(CI)1.98-6.23],pseudophakia/aphakia status[OR 2.74,95%CI(1.50-4.98)],multiple retinal breaks[OR 1.67,95%CI(1.03-2.70)],and a substantial extent of RRD[OR 11.58,95%CI(7.12-18.84)]were independent risk factors for RRDCD.CONCLUSION:Emergency surgical pattern of RRD demonstrates a lower incidence of RRDCD.The adoption of an expedited surgical approach has the potential to reduce the duration of RRD,possibly correlating with a decreased risk of RRDCD development.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
