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
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
Zinc oxide(ZnO)serves as a crucial functional semiconductor with a wide direct bandgap of approximately 3.37 eV.Solvothermal reaction is commonly used in the synthesis of ZnO micro/nanostructures,given its low cost,si...Zinc oxide(ZnO)serves as a crucial functional semiconductor with a wide direct bandgap of approximately 3.37 eV.Solvothermal reaction is commonly used in the synthesis of ZnO micro/nanostructures,given its low cost,simplicity,and easy implementation.Moreover,ZnO morphology engineering has become desirable through the alteration of minor conditions in the reaction process,particularly at room temperature.In this work,ZnO micro/nanostructures were synthesized in a solution by varying the amounts of the ammonia added at low temperatures(including room temperature).The formation of Zn^(2+)complexes by ammonia in the precursor regulated the reaction rate of the morphology engineering of ZnO,which resulted in various structures,such as nanoparticles,nanosheets,microflowers,and single crystals.Finally,the obtained ZnO was used in the optoelectronic application of ultraviolet detectors.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
Introduction: the left atrial appendage, a dormant embryonic vestige, would play a major role in cardiac hemodynamic changes, volume homeostasis and thrombi formation. It, therefore constitutes a therapeutic target. I...Introduction: the left atrial appendage, a dormant embryonic vestige, would play a major role in cardiac hemodynamic changes, volume homeostasis and thrombi formation. It, therefore constitutes a therapeutic target. Its morphology is extremely variable. Objective: it consisted on determining the morphological variations of the left auricle as well as their interest in the prevention of thrombi in the Senegalese. Material and Method: This study was conducted by dissecting 36 fresh hearts from Senegalese anatomical subjects with a sampling of the left atrial appendage, including specimens with normal morphological appearance. Their morphology was studied using the fresh and frozen plaster molding method. The data obtained were analyzed statistically. Results: the average age of the subjects was 33 years, with a sex ratio of 1.06, the cauliflower shape was dominant with 57% of cases and the cactus shape (4%) was less frequent. The cauliflower shape presented a clear angulation compared to the others without statistically significant differences according to age. Conclusion: This work showed a great morphological variability of the left atrial appendage. It can provide an update on the specificity of Senegalese. Taking these variations into account is important in the safe management of hemodynamic conditions and the improvement of the management of recurrent strokes.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
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
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
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
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
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
The preferential oxidation of CO(CO-PROX)reaction is a cost-effective method for eliminating trace amounts of CO from the fuel H2.Pt-based catalysts have been extensively studied for COPROX,with their activity influen...The preferential oxidation of CO(CO-PROX)reaction is a cost-effective method for eliminating trace amounts of CO from the fuel H2.Pt-based catalysts have been extensively studied for COPROX,with their activity influenced by the morphology of the support.Hydrothermal synthesis was employed to produce different morphologies ofγ-Al_(2)O_(3):flower-likeγ-Al_(2)O_(3)(f)exposing(110)crystal faces,sheet-likeγ-Al_(2)O_(3)(s)revealing(100)crystal faces,and rod-likeγ-Al_(2)O_(3)(r)displaying(111)crystal faces,followed by loading PtCo nanoparticles.The exposed crystal faces of the support impact the alloying degree of the PtCo nanoparticles,and an increase in the alloying degree correlates with enhanced catalyst reactivity.Pt_(3)Co intermetallic compounds were identified onγ-Al_(2)O_(3)(f)exposing(110)crystal faces,and PtCo/γ-Al_(2)O_(3)(f)showed high catalytic activity in the CO-PROX reaction,achieving 100%CO conversion across a broad temperature range of 50−225°C.In contrast,only partial alloying of PtCo was observed onγ-Al_(2)O_(3)(s).Furthermore,no alloying between Pt and Co occurred in PtCo/γ-Al_(2)O_(3)(r),resulting in a reaction rate at 50°C that was merely 11%of that of PtCo/γ-Al_(2)O_(3)(f).The formation of Pt3Co intermetallic compounds led to a more oxidized state of Pt,which significantly diminished the adsorption of CO on Pt and augmented the active oxygen species,thereby facilitating the selective oxidation of CO.展开更多
BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of va...BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.展开更多
Physical exercise is recognized as an effective intervention to improve mood,physical performance,and general well-being.It achieves these benefits through cellular and molecular mechanisms that promote the release of...Physical exercise is recognized as an effective intervention to improve mood,physical performance,and general well-being.It achieves these benefits through cellular and molecular mechanisms that promote the release of neuroprotective factors.Interestingly,reduced levels of physical exercise have been implicated in several central nervous system diseases,including ocular disorders.Emerging evidence has suggested that physical exercise levels are significantly lower in individuals with ocular diseases such as glaucoma,age-related macular degeneration,retinitis pigmentosa,and diabetic retinopathy.Physical exercise may have a neuroprotective effect on the retina.Therefore,the association between reduced physical exercise and ocular diseases may involve a bidirectional causal relationship whereby visual impairment leads to reduced physical exercise and decreased exercise exacerbates the development of ocular disease.In this review,we summarize the evidence linking physical exercise to eye disease and identify potential mediators of physical exercise-induced retinal neuroprotection.Finally,we discuss future directions for preclinical and clinical research in exercise and eye health.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
Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss a...Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.展开更多
AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHO...AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.展开更多
AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young pati...AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
基金supported by the 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funded by the National Natural Science F oundation of China(No.52172205)。
文摘Zinc oxide(ZnO)serves as a crucial functional semiconductor with a wide direct bandgap of approximately 3.37 eV.Solvothermal reaction is commonly used in the synthesis of ZnO micro/nanostructures,given its low cost,simplicity,and easy implementation.Moreover,ZnO morphology engineering has become desirable through the alteration of minor conditions in the reaction process,particularly at room temperature.In this work,ZnO micro/nanostructures were synthesized in a solution by varying the amounts of the ammonia added at low temperatures(including room temperature).The formation of Zn^(2+)complexes by ammonia in the precursor regulated the reaction rate of the morphology engineering of ZnO,which resulted in various structures,such as nanoparticles,nanosheets,microflowers,and single crystals.Finally,the obtained ZnO was used in the optoelectronic application of ultraviolet detectors.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
文摘Introduction: the left atrial appendage, a dormant embryonic vestige, would play a major role in cardiac hemodynamic changes, volume homeostasis and thrombi formation. It, therefore constitutes a therapeutic target. Its morphology is extremely variable. Objective: it consisted on determining the morphological variations of the left auricle as well as their interest in the prevention of thrombi in the Senegalese. Material and Method: This study was conducted by dissecting 36 fresh hearts from Senegalese anatomical subjects with a sampling of the left atrial appendage, including specimens with normal morphological appearance. Their morphology was studied using the fresh and frozen plaster molding method. The data obtained were analyzed statistically. Results: the average age of the subjects was 33 years, with a sex ratio of 1.06, the cauliflower shape was dominant with 57% of cases and the cactus shape (4%) was less frequent. The cauliflower shape presented a clear angulation compared to the others without statistically significant differences according to age. Conclusion: This work showed a great morphological variability of the left atrial appendage. It can provide an update on the specificity of Senegalese. Taking these variations into account is important in the safe management of hemodynamic conditions and the improvement of the management of recurrent strokes.
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.
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.
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 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.
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 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 National Natural Science Foundation of China(22376063,21976057)the Fund of the National Engineering Laboratory for Mobile Source Emission Control Technology(NELMS2020A05)Fundamental Research Funds for the Central Universities.
文摘The preferential oxidation of CO(CO-PROX)reaction is a cost-effective method for eliminating trace amounts of CO from the fuel H2.Pt-based catalysts have been extensively studied for COPROX,with their activity influenced by the morphology of the support.Hydrothermal synthesis was employed to produce different morphologies ofγ-Al_(2)O_(3):flower-likeγ-Al_(2)O_(3)(f)exposing(110)crystal faces,sheet-likeγ-Al_(2)O_(3)(s)revealing(100)crystal faces,and rod-likeγ-Al_(2)O_(3)(r)displaying(111)crystal faces,followed by loading PtCo nanoparticles.The exposed crystal faces of the support impact the alloying degree of the PtCo nanoparticles,and an increase in the alloying degree correlates with enhanced catalyst reactivity.Pt_(3)Co intermetallic compounds were identified onγ-Al_(2)O_(3)(f)exposing(110)crystal faces,and PtCo/γ-Al_(2)O_(3)(f)showed high catalytic activity in the CO-PROX reaction,achieving 100%CO conversion across a broad temperature range of 50−225°C.In contrast,only partial alloying of PtCo was observed onγ-Al_(2)O_(3)(s).Furthermore,no alloying between Pt and Co occurred in PtCo/γ-Al_(2)O_(3)(r),resulting in a reaction rate at 50°C that was merely 11%of that of PtCo/γ-Al_(2)O_(3)(f).The formation of Pt3Co intermetallic compounds led to a more oxidized state of Pt,which significantly diminished the adsorption of CO on Pt and augmented the active oxygen species,thereby facilitating the selective oxidation of CO.
文摘BACKGROUND Central retinal artery occlusion(CRAO)is a potentially blinding disease,and hyperbaric oxygen therapy(HBOT)is becoming increasingly popular with the support of scientific evidence.Despite the presence of various acute management measures,there is no clear evidence on the gold standard treatment for CRAO.AIM To identify factors and imaging parameters associated with good visual outcome,which guide ophthalmologists in the triage of CRAO patients for HBOT.METHODS Patients who suffered from CRAO and had a symptom onset≤6 h were recruited for a course of HBOT in a tertiary hospital after failing bedside treatment.Patient demographics,onset time,CRAO eye parameters,and past medical history were prospectively collected.Visual outcomes after HBOT were also analyzed.RESULTS A total of 26 patients were included;the female-to-male ratio was 1:1.6,and the mean age was 67.5 years±13.3 years(range 44–89 years).The mean duration of follow-up and mean visual acuity(VA)improvement were 10.0 mo±5.3 mo and 0.48 logarithm of minimal angle of resolution(logMAR)±0.57 logMAR(approx-imately 9 letters in ETDRS)(P=0.0001,Z=-3.67),respectively.The 1 mm zone of central macular thickness(CMT)on optical coherence tomography was not associated with VA changes(P=0.119);however,the 1-to-3 mm circular rim of CMT was fairly associated(P=0.02,Spearman's coefficient=0.45).Complete retinal perfusion time during fundus fluorescein angiography(FFA)was mode-rately associated(P=0.01,Spearman's coefficient=0.58)with visual outcome.
基金supported by the InnoHK Initiative and the Hong Kong Special Administrative Region Government, China (to SYY)。
文摘Physical exercise is recognized as an effective intervention to improve mood,physical performance,and general well-being.It achieves these benefits through cellular and molecular mechanisms that promote the release of neuroprotective factors.Interestingly,reduced levels of physical exercise have been implicated in several central nervous system diseases,including ocular disorders.Emerging evidence has suggested that physical exercise levels are significantly lower in individuals with ocular diseases such as glaucoma,age-related macular degeneration,retinitis pigmentosa,and diabetic retinopathy.Physical exercise may have a neuroprotective effect on the retina.Therefore,the association between reduced physical exercise and ocular diseases may involve a bidirectional causal relationship whereby visual impairment leads to reduced physical exercise and decreased exercise exacerbates the development of ocular disease.In this review,we summarize the evidence linking physical exercise to eye disease and identify potential mediators of physical exercise-induced retinal neuroprotection.Finally,we discuss future directions for preclinical and clinical research in exercise and eye health.
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 National Natural Science Foundation of China(No.82070964)Shaanxi Provincial Outstanding Youth Science Foundation Project(No.2022JC-60)+1 种基金Shaanxi International Science and Technology Cooperation Program Project(No.2024GHYBXM-20)Shaanxi Provincial Education Department Youth Innovation Team Research Project(No.23JP151).
文摘Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.
基金Supported by the National Natural Science Foundation of China(No.82171076,No.U22A20311,No.82388101)the National Key R&D Program(No.2022YFC2502800)Shanghai Municipal Education Commission(No.2023KJ05-67).
文摘AIM:To investigate whether interleukin-17A(IL-17A)gets involved in the mechanisms of inflammation-related retinal pigment epithelium(RPE)cells injury and its significance in age-related macular degeneration(AMD).MRTHODS:A sodium iodate(NaIO3)mouse model as well as IL-17A-/-mice were established.The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro,were investigated using immunofluorescence,immunoprotein blotting,and quantitative real-time fluorescence polymerase chain reaction(qRT-PCR),respectively.Interventions using recombinant IL-17A protein(rIL-17A)or IL-17A neutralizing antibody(IL-17A NAb)were used to observe the subsequent differences in fundus,fundus photography and optical coherence tomography(OCT),cell viability,and expression of oxidative stress-related markers before and after modeling,and to screen for key signaling pathways.RESULTS:In the scenario of NaIO3 stimulation,RPE cells obviously tended to degenerate.Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice,whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A-/-mice.In addition,IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo.Meanwhile,the extracellular signalregulated kinase(ERK)signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo,as IL-17A induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.CONCLUSION:IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway.Inhibition of IL-17A may be a new potential target for dry AMD treatment.
基金Supported by Youth Cultivation Research Program of Beijing Road Medical Area,Xinjiang Military Region General Hospital,Xinjiang,China(No.2022jzbj105)Science and Technology Program of Urumqi Municipal Health and Wellness Commission(No.202360).
文摘AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.
