The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(...AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.展开更多
AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A...AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.展开更多
Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatm...Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.展开更多
AIM:To compare the tear film quantity and stability parameters in keratoconus(KCN)and normal eyes using test breakup time(TBUT),noninvasive TBUT(NITBUT),and Schirmer test.METHODS:All participants(n=166),including pati...AIM:To compare the tear film quantity and stability parameters in keratoconus(KCN)and normal eyes using test breakup time(TBUT),noninvasive TBUT(NITBUT),and Schirmer test.METHODS:All participants(n=166),including patients with KCN and age-matched healthy individuals with normal corneas,were recruited from those referred to Farabi Eye Hospital,Iran,in 2023.To better account for genetic and environmental factors,the control group comprised healthy individuals who were relatives of KCN patients and had normal corneal topography.Tear quantity parameters were evaluated in the following order:NITBUT,TBUT,and Schirmer tests.RESULTS:The mean age of cases in KCN(61.7%males)and normal(63.5%males)participants was 27.54±5.44y(range 19 to 38)and 27.52±5.63y(range 20 to 38),respectively(P=0.976).NIBUT,TBUT,and Schirmer’s tests were significantly lower in KCN group compared to normal controls(all P<0.001).The mean difference for NIBUT was-7.81s(P<0.001),and for TBUT was-7.61s(P<0.001).Schirmer test values were also significantly lower in the KCN group,with a mean difference of-5.61 mm compared to normal people(P<0.001).CONCLUSION:Our findings demonstrate significant tear film impairment in KCN.The reductions in NIBUT,TBUT and Schirmer scores highlight an underlying tear film dysfunction in KCN that extends beyond the morphological changes of the cornea.展开更多
Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating th...Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating this condition.Nevertheless,considering the vast amount of research that is currently being conducted,focusing on the utilization of TCM in the management of myopia,there is an urgent requirement for a thorough and comprehensive review.The review would serve to clarify the practical applications of TCM within this specific field,and it would also aim to elucidate the underlying mechanisms that are at play,providing a deeper understanding of how TCM principles can be effectively integrated into modern medical practices.Here,some modern medical pathogenesis of myopia and appropriate TCM techniques studies are summarized in the prevention and treatment of myopia.Further,we discussed the potential mechanisms and the future research directions of TCM against myopia.Identifying these mechanisms is crucial for understanding how TCM can be effectively utilized in this context.The combination of various TCM methods or the combination of traditional Chinese and Western medicine is of great significance for the prevention and control of myopia in the future.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 determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.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
AIM:To identify topographic determinants of the anterior chamber angle(ACA)in patients with keratoconus(KCN).METHODS:Four hundred and ten eyes of 294 patients with KCN were recruited for this study.First,complete ocul...AIM:To identify topographic determinants of the anterior chamber angle(ACA)in patients with keratoconus(KCN).METHODS:Four hundred and ten eyes of 294 patients with KCN were recruited for this study.First,complete ocular examinations were performed for all patients,including visual acuity measurement,refraction,and slit-lamp biomicroscopy.Then,all participants underwent corneal imaging by the Oculus Pentacam HR.RESULTS:The mean age of the participants was 32.40±8.52y(15-60y)and 69.5%of them were male.The mean ACA was 38.47°±5.75°(range:14.40°to 56.50°)in the whole sample,38.24°±6.00°in males,and 38.98°±5.11°in females(P=0.447).The mean ACA was significantly different among different groups of cone morphology,as patients with nipple cones showed the lowest mean ACA.Moreover,there were statistically significant differences in the mean ACA among different groups of cone locations,with patients having central cones exhibiting the lowest mean ACA(P<0.001).Anterior and posterior Q values were significantly,directly correlated with ACA(anterior Q:r=0.122,P=0.014,posterior Q:r=0.192,P<0.001).CONCLUSION:This study provides critical insights into the risk factors for ACA narrowing in KCN patients,which is essential for planning intraocular surgeries.Patients with nipple and central cones exhibited the most significant ACA narrowing.Additionally,more negative Q-values are associated with increased ACA narrowing,highlighting the need for targeted diagnostic and therapeutic strategies.展开更多
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in...Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.展开更多
Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially me...Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.展开更多
AIM:To measure the contrast sensitivity(CS)using computer-based Chart2020 software pre-and post-white light exposure with and without blue-blocking lenses(BBLs).METHODS:The study included participants aged 18 to 25y(n...AIM:To measure the contrast sensitivity(CS)using computer-based Chart2020 software pre-and post-white light exposure with and without blue-blocking lenses(BBLs).METHODS:The study included participants aged 18 to 25y(n=30 eyes),where baseline CS was measured before the experiment.Following this,the participants were exposed to two white light-emitting diodes(LEDs;450 lx each),placed at a 45-degree angle from the participant’s eye and 80 cm from the light source.All participants were randomly divided into three groups(BBL1-Placebo lens,BBL2-Crizal Prevencia,BBL3-Duravision)by sequential randomisation,which was double-blinded.Post-light exposure,the CS was measured monocularly with a calibrated computer-based CS Chart-2020 software at different log units.RESULTS:CS measured using Chart-2020 software at 0.8,1.5,6,12,and 18 cpd pre-and post-white LED exposure with and without BBLs showed a significant difference(P<0.05)in contrast threshold and log contrast at 6 cpd and 18 cpd(P<0.05)and showed no significant differences in 0.8,1.5,12 cpd(P>0.05).CONCLUSION:This study shows that exposure to white LEDs can diminish CS,while BBLs may ameliorate these negative effects.展开更多
AIM:To characterize the ocular surface characteristics in the Nepalese population across all age groups who have used digital screens for extended durations over several years.METHODS:In a cross-sectional,observationa...AIM:To characterize the ocular surface characteristics in the Nepalese population across all age groups who have used digital screens for extended durations over several years.METHODS:In a cross-sectional,observational study,144 digital screen users were assessed for dry eye disease(DED)using subjective and objective measures.The Ocular Surface Disease Index(OSDI)Questionnaire evaluated symptoms,followed by clinical assessments,including slit lamp biomicroscopy,tear breakup time(TBUT),Oxford Scheme grading,and Schirmer I test.DED was diagnosed if a patient had an OSDI score over 13 and at least two clinical signs(OSDI,Schirmer I test,or ocular staining).The prevalence of DED was calculated based on the proportion of patients meeting these criteria.RESULTS:Of the 144 participants(mean age:34.6±15.2y),78(54.2%)were female.The use of digital screens varied between 2-8h(mean duration:4.1±2.7h)per day.The mean OSDI score,TBUT score,and the Schirmer I scores were 22.7±10.5(max-min:24.4-20.9),6.8±4.2s(max-min:7.5-6.1),and 12.3±4.6 mm(max-min:13.1-11.5)respectively with 95%confidence interval(β=1.96),and a two-tailed statistical significance level of 5%(α=0.05).With increased screen use,TBUT shortened and OSDI scores increased significantly(P<0.01),though Schirmer I scores were unaffected(P>0.05).The prevalence of DED ranged from 6.3%to 22.9%in those using screens for more than 2h,with an overall prevalence of 67.4%among digital screen users.CONCLUSION:There is a significant association between prolonged use of digital screens and clinical markers of dry eye signs and symptoms.展开更多
Dear Editor,In this case,we discuss a teenager who experienced severe eye pain and elevated intraocular pressure(IOP)caused by reverse pupillary block,which was successfully resolved using Neodymium-doped yttrium alum...Dear Editor,In this case,we discuss a teenager who experienced severe eye pain and elevated intraocular pressure(IOP)caused by reverse pupillary block,which was successfully resolved using Neodymium-doped yttrium aluminum garnet(Nd:YAG)laser peripheral iridotomy(LPI).展开更多
AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen ...AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen participants,with a mean age of 24.5±4y,underwent choroidal thickness and vascularity index measurements using enhanced depth imaging optical coherence tomography(EDI OCT)at baseline,one day,and one week following MFGPCL wear.Two center-distance MFGPCL designs with similar center zone diameters of 3.0 mm but different peripheral add powers(low add:+1.5 D and high add:+3.0 D)were tested.Each participant was randomly assigned to wear one of the two MFGPCL designs.Measurements of total,luminal,and stromal choroid thickness were obtained in five eccentric regions(6 mm towards the periphery)in all quadrants.RESULTS:Significant thickening in total choroidal thickness were observed after one week of wearing both high add(+10±6µm)and low add(+7±5µm)MFGPCLs,with no statistically significant difference between the two groups(P=0.42).Choroidal thickening was consistent across eccentric regions and quadrants,with no significant differences based on eccentricity or quadrant(all P>0.05).Both lens designs induced choroidal thickening,with no significant difference between them in total choroidal thickness(P=0.18 for quadrants,P=0.51 for eccentric regions).CONCLUSION:Peripheral myopic defocus induced by MFGPCLs lead to significant choroidal thickening,including total,luminal,and stromal components.This study highlights the need for future research to explore the dose-response relationship between peripheral myopic defocus and choroidal thickening,utilizing choroidal response as a potential biomarker.展开更多
Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scoto...Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scotoma enlargement.Currently,there is no standardized treatment protocol for MacTel type 1[1-2].Treatment outcomes can vary significantly among individuals,highlighting the ongoing need for further exploration of new and more effective treatment options.This paper presents a case of refractory macular edema associated with MacTel type 1,which showed a favorable response to pars plana vitrectomy(PPV)and internal limiting membrane(ILM)peeling.展开更多
High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These ...High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These residual tumorous cells are most likely to cause tumorous recurrence.This article reports the preparation of a multifunctional nanocomposite which can be used to treat CM efficiently via a chemotherapyassisted-photothermal therapy(CTH-PTT).The nanocomposite comprises of alpha-tocopheryl succinate(α-TOS)and carboxylic chitosan modified graphene(CG).α-TOS has been potentially seen as an efficient CTH antitumor drug while its deficiency such as easy being hydrolyzed by gastrointestinal esterase and poor hydrophilicity inevitable limits the clinic application ofα-TOS.CG is introduced to overcome these shortcomings,offering additional advantages such as the PTT possibility for the antitumor application.The employment of CG-α-TOS on ocular CM cells caused more than 80%inhibition rates after irradiation under an 808 nm laser for 10 min.The outcomes of this work provide a facile and advantageous way to resolve the essential issue of the treatment of ocular tumors such as CM.展开更多
OBJECTIVE:To determine the mechanism of electroacupuncture(EA)effect by the wingless-related integration site(Wnt)/β-catenin pathway in the guinea pig myopia model.METHODS:Following myopia induction and EA,guinea pig...OBJECTIVE:To determine the mechanism of electroacupuncture(EA)effect by the wingless-related integration site(Wnt)/β-catenin pathway in the guinea pig myopia model.METHODS:Following myopia induction and EA,guinea pigs were treated with biometry to evaluate refraction and axial length.Hematoxylin and eosin(HE)staining was used to observe that the retina,choroid,and sclera had abnormal morphology.At 4,6,and 8 weeks,quantitative polymerase chain reaction(q PCR)was used to identify the expression of matrix metallopeptidase-2(MMP-2)/MMP-3/tissue inhibitor of metalloprotease-2(TIMP-2)/TIMP-3/Wnt family member 2B(WNT2B)/WNT3A/WNT7B/beta-catenin 1(CTNNB1),and dickkopf wnt signaling pathway inhibitor 1(DKK-1)m RNAs in the retina,choroid,and sclera.Western blot was used to detect the protein expression of WNT7B/2B/3A,CTNNB1 and DKK-1 in retina,choroid and sclera at 4 weeks.Enzyme-linked immunosorbent assay was used to detect the protein expression of MMP-2/TIMP-2 and MMP-3/TIMP-3 in serum at 4 weeks.Moreover,a DKK-1 inhibitor was injected into the vitreous cavity,and the expression of the above molecules was detected.RESULTS:EA could reduce the optic axial length and diopter and ameliorate ocular pathology,inhibited the expression of MMP-2/MMP-3 and WNT2B/WNT3A/WNT7B/CTNNB1,while increased the expression levels of TIMP-2/TIMP-3 and DKK-1.However,the expression levels of WNT2B/WNT3A/WNT7B/CTNNB1 and MMP-2/MMP-3 were significantly increased,and the TIMP-2/TIMP-3 and DKK-1 expression levels were decreased after injected DKK-1 inhibitor.CONCLUSION:The mechanism of EA's effects on myopia may involve the downregulation of the Wnt/β-catenin pathway and correct MMP-2/MMP-3/TIMP-2/TIMP-3 balance.展开更多
AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,...AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,18 cycles/degree).METHODS:A before-after study was conducted on 45 emmetropic students from Shahid Beheshti University of Medical Sciences.Visual acuity,contrast sensitivity,stereopsis and phoria were measured under three conditions:without sunglasses,with non-polarized sunglasses and with polarized sunglasses.Tests were conducted under controlled glare conditions to simulate outdoor environments.RESULTS:A total of 45 participants were evaluated,comprising 17 males(37.8%)and 28 females(62.2%).The mean age was 21.67±2.31y(range 18-27y).The mean of distance and near visual acuity in all three conditions were equal to 0.00 logMAR.Contrast sensitivity generally decreased slightly with the use of non-polarized sunglasses compared to the no-sunglasses condition.The mean stereopsis with polarized sunglasses was 101.33±56.139 arc sec,which was worse than the no-sunglasses condition(94.33±46.632 arc sec)and better than the non-polarized sunglasses condition(105.67±58.965 arc sec),although these changes were not significant.In the phoria parameter,distance phoria appeared more affected than near phoria.CONCLUSION:Polarized and non-polarized sunglasses do not significantly affect visual acuity,stereopsis,or phoria under controlled glare conditions.Slight changes in contrast sensitivity are noted,but they are not statistically significant.展开更多
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
文摘AIM:To report and analyze cases of sterile intraocular inflammation(IOI)following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration(nAMD)and diabetic macular edema(DME).METHODS:This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy.Comprehensive clinical evaluation was performed,including slit-lamp examination,intraocular pressure(IOP)measurement,fluorescein and indocyanine green angiography(ICGA),and laboratory tests.Inflammatory responses were treated with topical or systemic corticosteroids,and patients were monitored for visual acuity and inflammatory activity.RESULTS:The incidence of IOI was 0.8%per patient(Innsbruck)and 0.23%(Czechia),with inflammation typically occurring between the third and sixth injection(mean interval:10d post-injection).Inflammator y presentations ranged from anterior uveitis to posterior segment involvement.One notable case demonstrated novel choroidal hypofluorescent lesions on angiography,suggesting deeper ocular involvement.The mean patient age was 76y;five of six affected patients were female.All cases responded to local and systemic corticosteroids,with full recovery of initial visual acuity.CONCLUSION:Sterile IOI after faricimab appears to be a rare but relevant adverse event.Although the incidence falls within expected ranges for anti-vascular endothelial growth factor(anti-VEGF)agents,the observed choroidal involvement represents a potentially new safety signal.Prompt diagnosis and corticosteroid therapy are effective in all cases.Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.
基金Supported by Ongoing Research Funding Program(ORFFT-2025-054-1),King Saud University,Riyadh,Saudi Arabia.
文摘AIM:To evaluate the efficacy of the total computer vision syndrome questionnaire(CVS-Q)score as a predictive tool for identifying individuals with symptomatic binocular vision anomalies and refractive errors.METHODS:A total of 141 healthy computer users underwent comprehensive clinical visual function assessments,including evaluations of refractive errors,accommodation(amplitude of accommodation,positive relative accommodation,negative relative accommodation,accommodative accuracy,and accommodative facility),and vergence(phoria,positive and negative fusional vergence,near point of convergence,and vergence facility).Total CVS-Q scores were recorded to explore potential associations between symptom scores and the aforementioned clinical visual function parameters.RESULTS:The cohort included 54 males(38.3%)with a mean age of 23.9±0.58y and 87 age-matched females(61.7%)with a mean age of 23.9±0.53y.The multiple regression model was statistically significant[R²=0.60,F=13.28,degrees of freedom(DF=17122,P<0.001].This indicates that 60%of the variance in total CVS-Q scores(reflecting reported symptoms)could be explained by four clinical measurements:amplitude of accommodation,positive relative accommodation,exophoria at distance and near,and positive fusional vergence at near.CONCLUSION:The total CVS-Q score is a valid and reliable tool for predicting the presence of various nonstrabismic binocular vision anomalies and refractive errors in symptomatic computer users.
基金supported by a Ph.D.scholarship from the YLSY program of the Republic of Turkiye,Ministry of National Educationfunded by Fight for Sight UK,grant reference#5183/5184。
文摘Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.
文摘AIM:To compare the tear film quantity and stability parameters in keratoconus(KCN)and normal eyes using test breakup time(TBUT),noninvasive TBUT(NITBUT),and Schirmer test.METHODS:All participants(n=166),including patients with KCN and age-matched healthy individuals with normal corneas,were recruited from those referred to Farabi Eye Hospital,Iran,in 2023.To better account for genetic and environmental factors,the control group comprised healthy individuals who were relatives of KCN patients and had normal corneal topography.Tear quantity parameters were evaluated in the following order:NITBUT,TBUT,and Schirmer tests.RESULTS:The mean age of cases in KCN(61.7%males)and normal(63.5%males)participants was 27.54±5.44y(range 19 to 38)and 27.52±5.63y(range 20 to 38),respectively(P=0.976).NIBUT,TBUT,and Schirmer’s tests were significantly lower in KCN group compared to normal controls(all P<0.001).The mean difference for NIBUT was-7.81s(P<0.001),and for TBUT was-7.61s(P<0.001).Schirmer test values were also significantly lower in the KCN group,with a mean difference of-5.61 mm compared to normal people(P<0.001).CONCLUSION:Our findings demonstrate significant tear film impairment in KCN.The reductions in NIBUT,TBUT and Schirmer scores highlight an underlying tear film dysfunction in KCN that extends beyond the morphological changes of the cornea.
基金supported by Healthy China initiative of Traditional Chinese Medicine(No.889042).
文摘Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating this condition.Nevertheless,considering the vast amount of research that is currently being conducted,focusing on the utilization of TCM in the management of myopia,there is an urgent requirement for a thorough and comprehensive review.The review would serve to clarify the practical applications of TCM within this specific field,and it would also aim to elucidate the underlying mechanisms that are at play,providing a deeper understanding of how TCM principles can be effectively integrated into modern medical practices.Here,some modern medical pathogenesis of myopia and appropriate TCM techniques studies are summarized in the prevention and treatment of myopia.Further,we discussed the potential mechanisms and the future research directions of TCM against myopia.Identifying these mechanisms is crucial for understanding how TCM can be effectively utilized in this context.The combination of various TCM methods or the combination of traditional Chinese and Western medicine is of great significance for the prevention and control of myopia in the future.
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 grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
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 Iranian University of Medical Sciences(code:IR.IUMS.REC.1401.371).
文摘AIM:To identify topographic determinants of the anterior chamber angle(ACA)in patients with keratoconus(KCN).METHODS:Four hundred and ten eyes of 294 patients with KCN were recruited for this study.First,complete ocular examinations were performed for all patients,including visual acuity measurement,refraction,and slit-lamp biomicroscopy.Then,all participants underwent corneal imaging by the Oculus Pentacam HR.RESULTS:The mean age of the participants was 32.40±8.52y(15-60y)and 69.5%of them were male.The mean ACA was 38.47°±5.75°(range:14.40°to 56.50°)in the whole sample,38.24°±6.00°in males,and 38.98°±5.11°in females(P=0.447).The mean ACA was significantly different among different groups of cone morphology,as patients with nipple cones showed the lowest mean ACA.Moreover,there were statistically significant differences in the mean ACA among different groups of cone locations,with patients having central cones exhibiting the lowest mean ACA(P<0.001).Anterior and posterior Q values were significantly,directly correlated with ACA(anterior Q:r=0.122,P=0.014,posterior Q:r=0.192,P<0.001).CONCLUSION:This study provides critical insights into the risk factors for ACA narrowing in KCN patients,which is essential for planning intraocular surgeries.Patients with nipple and central cones exhibited the most significant ACA narrowing.Additionally,more negative Q-values are associated with increased ACA narrowing,highlighting the need for targeted diagnostic and therapeutic strategies.
基金supported by grants from the Wenzhou Science and Technology Bureau Foundation,China(Grant No.:ZY2019014)“Pioneer”and“Leading Goose”R&D Program of Zhejiang,China(Grant No.:2022C03144)National Natural Science Foundation of China(Grant Nos.:82172494,and 82372461).
文摘Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
文摘Dry eye disease(DED)is a multifactorial disorder that disturbs ocular surface equilibrium,considerably diminishing quality of life.Present therapies only offer symptomatic alleviation.Stem cell treatment,especially mesenchymal stem cells(MSCs),has surfaced as a viable approach for tissue regeneration and immunological regulation in DED.Preclinical and early clinical investigations indicate that MSCs can improve lacrimal gland functionality,diminish inflammation,and facilitate corneal regeneration.Nonetheless,obstacles persist in enhancing MSC viability,determining the optimal MSC source,and guaranteeing sustained therapeutic effectiveness.Additional extensive randomized clinical trials are required to confirm the efficacy of MSC-based therapies for severe DED.
文摘AIM:To measure the contrast sensitivity(CS)using computer-based Chart2020 software pre-and post-white light exposure with and without blue-blocking lenses(BBLs).METHODS:The study included participants aged 18 to 25y(n=30 eyes),where baseline CS was measured before the experiment.Following this,the participants were exposed to two white light-emitting diodes(LEDs;450 lx each),placed at a 45-degree angle from the participant’s eye and 80 cm from the light source.All participants were randomly divided into three groups(BBL1-Placebo lens,BBL2-Crizal Prevencia,BBL3-Duravision)by sequential randomisation,which was double-blinded.Post-light exposure,the CS was measured monocularly with a calibrated computer-based CS Chart-2020 software at different log units.RESULTS:CS measured using Chart-2020 software at 0.8,1.5,6,12,and 18 cpd pre-and post-white LED exposure with and without BBLs showed a significant difference(P<0.05)in contrast threshold and log contrast at 6 cpd and 18 cpd(P<0.05)and showed no significant differences in 0.8,1.5,12 cpd(P>0.05).CONCLUSION:This study shows that exposure to white LEDs can diminish CS,while BBLs may ameliorate these negative effects.
文摘AIM:To characterize the ocular surface characteristics in the Nepalese population across all age groups who have used digital screens for extended durations over several years.METHODS:In a cross-sectional,observational study,144 digital screen users were assessed for dry eye disease(DED)using subjective and objective measures.The Ocular Surface Disease Index(OSDI)Questionnaire evaluated symptoms,followed by clinical assessments,including slit lamp biomicroscopy,tear breakup time(TBUT),Oxford Scheme grading,and Schirmer I test.DED was diagnosed if a patient had an OSDI score over 13 and at least two clinical signs(OSDI,Schirmer I test,or ocular staining).The prevalence of DED was calculated based on the proportion of patients meeting these criteria.RESULTS:Of the 144 participants(mean age:34.6±15.2y),78(54.2%)were female.The use of digital screens varied between 2-8h(mean duration:4.1±2.7h)per day.The mean OSDI score,TBUT score,and the Schirmer I scores were 22.7±10.5(max-min:24.4-20.9),6.8±4.2s(max-min:7.5-6.1),and 12.3±4.6 mm(max-min:13.1-11.5)respectively with 95%confidence interval(β=1.96),and a two-tailed statistical significance level of 5%(α=0.05).With increased screen use,TBUT shortened and OSDI scores increased significantly(P<0.01),though Schirmer I scores were unaffected(P>0.05).The prevalence of DED ranged from 6.3%to 22.9%in those using screens for more than 2h,with an overall prevalence of 67.4%among digital screen users.CONCLUSION:There is a significant association between prolonged use of digital screens and clinical markers of dry eye signs and symptoms.
文摘Dear Editor,In this case,we discuss a teenager who experienced severe eye pain and elevated intraocular pressure(IOP)caused by reverse pupillary block,which was successfully resolved using Neodymium-doped yttrium aluminum garnet(Nd:YAG)laser peripheral iridotomy(LPI).
基金Supported by Ongoing Research Funding Program(No.ORF-2025-1160),King Saud University,Riyadh Saudi Arabia.
文摘AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen participants,with a mean age of 24.5±4y,underwent choroidal thickness and vascularity index measurements using enhanced depth imaging optical coherence tomography(EDI OCT)at baseline,one day,and one week following MFGPCL wear.Two center-distance MFGPCL designs with similar center zone diameters of 3.0 mm but different peripheral add powers(low add:+1.5 D and high add:+3.0 D)were tested.Each participant was randomly assigned to wear one of the two MFGPCL designs.Measurements of total,luminal,and stromal choroid thickness were obtained in five eccentric regions(6 mm towards the periphery)in all quadrants.RESULTS:Significant thickening in total choroidal thickness were observed after one week of wearing both high add(+10±6µm)and low add(+7±5µm)MFGPCLs,with no statistically significant difference between the two groups(P=0.42).Choroidal thickening was consistent across eccentric regions and quadrants,with no significant differences based on eccentricity or quadrant(all P>0.05).Both lens designs induced choroidal thickening,with no significant difference between them in total choroidal thickness(P=0.18 for quadrants,P=0.51 for eccentric regions).CONCLUSION:Peripheral myopic defocus induced by MFGPCLs lead to significant choroidal thickening,including total,luminal,and stromal components.This study highlights the need for future research to explore the dose-response relationship between peripheral myopic defocus and choroidal thickening,utilizing choroidal response as a potential biomarker.
基金Supported by Science and Technology Project of Sichuan Provincial Health Commission(No.24WXXT13)North Sichuan Medical College Doctor Start-up Fund Project(No.CBY24-QDA01).
文摘Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scotoma enlargement.Currently,there is no standardized treatment protocol for MacTel type 1[1-2].Treatment outcomes can vary significantly among individuals,highlighting the ongoing need for further exploration of new and more effective treatment options.This paper presents a case of refractory macular edema associated with MacTel type 1,which showed a favorable response to pars plana vitrectomy(PPV)and internal limiting membrane(ILM)peeling.
基金financially supported by the National Natural Science Foundation of China(Nos.82202354,U20A20338)the Summit Advancement Disciplines of Zhejiang Province(Wenzhou Medical University Pharmaceutics)Key R&D Program of Zhejiang Province(No.2021C04019)。
文摘High mortality of choroidal melanoma(CM)is mainly attributed to the high likelihood of tumorous recurrence.The essential challenge lies in the presence of residual CM cells survived from the antitumor treatment.These residual tumorous cells are most likely to cause tumorous recurrence.This article reports the preparation of a multifunctional nanocomposite which can be used to treat CM efficiently via a chemotherapyassisted-photothermal therapy(CTH-PTT).The nanocomposite comprises of alpha-tocopheryl succinate(α-TOS)and carboxylic chitosan modified graphene(CG).α-TOS has been potentially seen as an efficient CTH antitumor drug while its deficiency such as easy being hydrolyzed by gastrointestinal esterase and poor hydrophilicity inevitable limits the clinic application ofα-TOS.CG is introduced to overcome these shortcomings,offering additional advantages such as the PTT possibility for the antitumor application.The employment of CG-α-TOS on ocular CM cells caused more than 80%inhibition rates after irradiation under an 808 nm laser for 10 min.The outcomes of this work provide a facile and advantageous way to resolve the essential issue of the treatment of ocular tumors such as CM.
基金Supported by the National Natural Youth Science Foundation:Research on the Mechanism of Acupuncture in Modulating the Inflammatory Microenvironment via the Muscarinic Acetylcholine Receptor(mAChR1)Signaling Pathway for Myopia Intervention(82205198)China Postdoctoral Science Foundation Project:Research on the Mechanism of Acupuncture in Modulating the Inflammatory Microenvironment via the mAChR1 Signaling Pathway for Myopia Intervention(2022M711984)+5 种基金Shandong Provincial Natural Science Foundation General Program:to Investigate the Underlying Mechanism of Acupuncture in Treating Myopia Associated eith Kidney Yang Deficiency Syndrome through the Muscarinic Acetylcholine Receptors(M-AChRs)Signaling Pathway(ZR2020MH393)Postdoctoral Innovation Project of Shandong Province:Research on the Mechanism of Electroacupuncture in Treating Myopia with"Kidney Yang Deficiency Syndrome"through the M-AChRs/Gamma-Aminobutyric Acid Signaling Pathway(202101012)China Postdoctoral Foundation General Program:to Investigate the Underlying Mechanism of Acupuncture in Treating Myopia Associated with Kidney Yang Deficiency Syndrome through the M-AChRs Signaling Pathway(2020M672127)National Natural Science Foundation:Research on the Influence of Acupuncture on the Accommodative Function and Visual Cortex Functional Network of Myopia and its Mechanism(82074498)National Key R&D Project:National Key Research and Development Program"Basic Research on High Myopia"(2019YFC1710200)National Natural Science Foundation of China:Research on the Relationship between Lens-Induced Myopia based on Omics Technology and Traditional Chinese Medicine Syndrome Types and its Molecular Mechanism(82474579)。
文摘OBJECTIVE:To determine the mechanism of electroacupuncture(EA)effect by the wingless-related integration site(Wnt)/β-catenin pathway in the guinea pig myopia model.METHODS:Following myopia induction and EA,guinea pigs were treated with biometry to evaluate refraction and axial length.Hematoxylin and eosin(HE)staining was used to observe that the retina,choroid,and sclera had abnormal morphology.At 4,6,and 8 weeks,quantitative polymerase chain reaction(q PCR)was used to identify the expression of matrix metallopeptidase-2(MMP-2)/MMP-3/tissue inhibitor of metalloprotease-2(TIMP-2)/TIMP-3/Wnt family member 2B(WNT2B)/WNT3A/WNT7B/beta-catenin 1(CTNNB1),and dickkopf wnt signaling pathway inhibitor 1(DKK-1)m RNAs in the retina,choroid,and sclera.Western blot was used to detect the protein expression of WNT7B/2B/3A,CTNNB1 and DKK-1 in retina,choroid and sclera at 4 weeks.Enzyme-linked immunosorbent assay was used to detect the protein expression of MMP-2/TIMP-2 and MMP-3/TIMP-3 in serum at 4 weeks.Moreover,a DKK-1 inhibitor was injected into the vitreous cavity,and the expression of the above molecules was detected.RESULTS:EA could reduce the optic axial length and diopter and ameliorate ocular pathology,inhibited the expression of MMP-2/MMP-3 and WNT2B/WNT3A/WNT7B/CTNNB1,while increased the expression levels of TIMP-2/TIMP-3 and DKK-1.However,the expression levels of WNT2B/WNT3A/WNT7B/CTNNB1 and MMP-2/MMP-3 were significantly increased,and the TIMP-2/TIMP-3 and DKK-1 expression levels were decreased after injected DKK-1 inhibitor.CONCLUSION:The mechanism of EA's effects on myopia may involve the downregulation of the Wnt/β-catenin pathway and correct MMP-2/MMP-3/TIMP-2/TIMP-3 balance.
文摘AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,18 cycles/degree).METHODS:A before-after study was conducted on 45 emmetropic students from Shahid Beheshti University of Medical Sciences.Visual acuity,contrast sensitivity,stereopsis and phoria were measured under three conditions:without sunglasses,with non-polarized sunglasses and with polarized sunglasses.Tests were conducted under controlled glare conditions to simulate outdoor environments.RESULTS:A total of 45 participants were evaluated,comprising 17 males(37.8%)and 28 females(62.2%).The mean age was 21.67±2.31y(range 18-27y).The mean of distance and near visual acuity in all three conditions were equal to 0.00 logMAR.Contrast sensitivity generally decreased slightly with the use of non-polarized sunglasses compared to the no-sunglasses condition.The mean stereopsis with polarized sunglasses was 101.33±56.139 arc sec,which was worse than the no-sunglasses condition(94.33±46.632 arc sec)and better than the non-polarized sunglasses condition(105.67±58.965 arc sec),although these changes were not significant.In the phoria parameter,distance phoria appeared more affected than near phoria.CONCLUSION:Polarized and non-polarized sunglasses do not significantly affect visual acuity,stereopsis,or phoria under controlled glare conditions.Slight changes in contrast sensitivity are noted,but they are not statistically significant.
