Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for th...Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.展开更多
Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its cons...Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its consistency,ease of use,and good quality in extensive clinical practice.In this study,a convolutional neural network(CSPDarknet53)was combined with a transformer to construct a new hybrid model,HCSP-Net.This hybrid model was employed to tri-classify color fundus photography into the normal macula(NM),dry macular degeneration(DMD),and wet macular degeneration(WMD)based on clinical classification manifestations,thus identifying and resolving AMD as early as possible with color fundus photography.To further enhance the performance of this model,grouped convolution was introduced in this study without significantly increasing the number of parameters.HCSP-Net was validated using an independent test set.The average precision of HCSPNet in the diagnosis of AMD was 99.2%,the recall rate was 98.2%,the F1-Score was 98.7%,the PPV(positive predictive value)was 99.2%,and the NPV(negative predictive value)was 99.6%.Moreover,a knowledge distillation approach was also adopted to develop a lightweight student network(SCSP-Net).The experimental results revealed a noteworthy enhancement in the accuracy of SCSP-Net,rising from 94%to 97%,while remarkably reducing the parameter count to a quarter of HCSP-Net.This attribute positions SCSP-Net as a highly suitable candidate for the deployment of resource-constrained devices,which may provide ophthalmologists with an efficient tool for diagnosing AMD.展开更多
Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomer...Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.展开更多
Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress o...Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.展开更多
AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB...AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB respectively.The MTT assay was utilized to evaluate cell proliferation.Flow cytometry was employed for analysis of cell apoptosis and cell cycle.COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence.The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by RT-PCR.RESULTS:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 phase.COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls.Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure.Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite trend.Results from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group.CONCLUSION:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.展开更多
BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of di...BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.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
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
针对从视频中恢复三维人体模型运动序列时,由于图像特征提取能力有限而导致三维人体模型运动序列重建效果不佳的问题,提出了一种基于Involution卷积的三维人体重建方法。首先为了引入自注意力机制,在ResNet50网络结构中加入Involution算...针对从视频中恢复三维人体模型运动序列时,由于图像特征提取能力有限而导致三维人体模型运动序列重建效果不佳的问题,提出了一种基于Involution卷积的三维人体重建方法。首先为了引入自注意力机制,在ResNet50网络结构中加入Involution算子,获取视频图像帧的特征向量,然后使用姿态估计网络和形状估计网络获取人体姿势以及形状参数,最后使用蒙皮多人线性模型(skinned multi-person linear model, SMPL)生成三维人体模型的运动序列。在三维姿态户外数据集(3D pose in the wild, 3DPW)上与视频人体姿态形状估计推理(video inference for body pose and shape estimation, VIBE)方法以及时间一致性网格恢复(temporally consistent mesh recovery, TCMR)方法进行对比实验,平均精度相比于VIBE、TCMR分别提升了3.1%、0.7%,能够为运动捕捉、三维人体动画制作等工作提供更为准确的三维人体模型。展开更多
Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascula...Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.展开更多
AIM:To develop and validate a questionnaire to evaluate knowledge,attitude and practice of patients diagnosed with age-related macular degeneration(AMD)who have undergone intravitreal injection treatment.METHODS:This ...AIM:To develop and validate a questionnaire to evaluate knowledge,attitude and practice of patients diagnosed with age-related macular degeneration(AMD)who have undergone intravitreal injection treatment.METHODS:This study was conducted among patients diagnosed with AMD in Kuala Lumpur.The generation of the instrument included four phases which included item and domains development,content,face validity and exploratory factor analysis.Content validity and modified Kappa was used for validation of knowledge domain.Exploratory factor analysis was used for validation of both attitude and practice domains.Face validity was conducted in 12 patients,content validity was ascertained in 120 patients and test-retest reliability was determined in 39 patients with AMD.RESULTS:Content validity index(CVI)and modified kappa showed excellent values for most items in the knowledge domain with CVI for item(I-CVI)values between 0.78-1.0 and Kappa values of>0.74.The Kaiser-MeyerOlkin(KMO)sampling adequacy showed acceptable scores of 0.70 and 0.75 for both attitude and practice domains respectively and Bartlett’s Test of sphericity were significant(χ^(2)=0.00,P<0.001).Factor analysis resulted in five factors with thirty items for attitude domain and four factors with twenty items for practice domain.The Cronbach’s alpha showed acceptable values for all items in knowledge,attitude and practice domain with values>0.70 and good test-retest reliability.The final version of the questionnaire consisted of 93 items from four sections consisting of demographic details,knowledge,attitude and practice.CONCLUSION:The findings of this validation and reliability study show that the developed questionnaire has a satisfactory psychometric property for measuring KAP of patients diagnosed with AMD undergoing intravitreal injection treatment.展开更多
Patients with age-related hearing loss face hearing difficulties in daily life.The causes of age-related hearing loss are complex and include changes in peripheral hearing,central processing,and cognitive-related abil...Patients with age-related hearing loss face hearing difficulties in daily life.The causes of age-related hearing loss are complex and include changes in peripheral hearing,central processing,and cognitive-related abilities.Furthermore,the factors by which aging relates to hearing loss via changes in audito ry processing ability are still unclear.In this cross-sectional study,we evaluated 27 older adults(over 60 years old) with age-related hearing loss,21 older adults(over 60years old) with normal hearing,and 30 younger subjects(18-30 years old) with normal hearing.We used the outcome of the uppe r-threshold test,including the time-compressed thres h old and the speech recognition threshold in noisy conditions,as a behavioral indicator of auditory processing ability.We also used electroencephalogra p hy to identify presbycusis-related abnormalities in the brain while the participants were in a spontaneous resting state.The timecompressed threshold and speech recognition threshold data indicated significant diffe rences among the groups.In patients with age-related hearing loss,information masking(babble noise) had a greater effect than energy masking(speech-shaped noise) on processing difficulties.In terms of resting-state electroencephalography signals,we observed enhanced fro ntal lobe(Brodmann’s area,BA11) activation in the older adults with normal hearing compared with the younger participants with normal hearing,and greater activation in the parietal(BA7) and occipital(BA19) lobes in the individuals with age-related hearing loss compared with the younger adults.Our functional connection analysis suggested that compared with younger people,the older adults with normal hearing exhibited enhanced connections among networks,including the default mode network,sensorimotor network,cingulo-opercular network,occipital network,and frontoparietal network.These results suggest that both normal aging and the development of age-related hearing loss have a negative effect on advanced audito ry processing capabilities and that hearing loss accele rates the decline in speech comprehension,especially in speech competition situations.Older adults with normal hearing may have increased compensatory attentional resource recruitment represented by the to p-down active listening mechanism,while those with age-related hearing loss exhibit decompensation of network connections involving multisensory integration.展开更多
Age-related macular degeneration is a major global cause of central visual impairment and seve re vision loss.With an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ...Age-related macular degeneration is a major global cause of central visual impairment and seve re vision loss.With an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ctor treatment is likely to increase.In addition,current conventional treatment is only available for the late neovascular stage of age-related macular degeneration,and injections can come with potentially devastating complications,introducing the need for more economical and ris kfree treatment.In recent years,exosomes,which are nano-sized extracellular vesicles of an endocytic origin,have shown immense potential as diagnostic biomarkers and in the therapeutic application,as they are bestowed with characte ristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells.Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases;however,exosomes as a potential therapy for seve ral retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically.This article will focus on the limited literature availa ble on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures,as well as briefly identify future research directions.Current literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury,N-methyl-N-nitrosourea,and royal college of surgeon models,which mimic inflammatory and degenerative aspects of agerelated macular degeneration.These have shown promising results in preserving retinal function and morphology,as well as protecting photoreceptors from apoptosis.Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cyto kines,mRNAs,and proteins involved in photo receptor degeneration pathways to exert a therapeutic effect.Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.展开更多
AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT...AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.展开更多
·AIM:To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor(VEGF)injections to treat neovascular agerelated macular degeneration(n AMD)with subretinal...·AIM:To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor(VEGF)injections to treat neovascular agerelated macular degeneration(n AMD)with subretinal fluid(SRF)and pigment epithelial detachment(PED).·METHODS:This prospective study included eyes with n AMD previously treated with as-needed anti-VEGF injections.The patients were treated with six monthly intravitreal injections of ranibizumab.Quantitative volumetric segmentation analyses of the SRF and PED were performed.The main outcome measures included best-corrected visual acuity(BCVA),and SRF and PED volumes.·RESULTS:Twenty eyes of 20 patients were included in this study.At the 6-month follow-up,BCVA and PED volume did not change significantly(P=0.110 and 0.999,respectively)but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3(P=0.002).The absorption rate of the SRF volume was negatively correlated with the duration of previous antiVEGF treatment(P=0.029).Seven of the 20 eyes(35%)showed a fluid-free macula and significant improvement in BCVA(P=0.036)by month 6.·CONCLUSION:Quantifying the SRF can precisely determine the patient’s responsiveness to anti-VEGF treatment of n AMD.展开更多
基金supported by the Ministry of Science and Innovation of Spain,"Instituto de Salud CarlosⅢ","Fon do de Investigacion Sanitaria" (PI19/00265)funds FEDER"Una manera de hacer Europa" (to BM)。
文摘Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.
基金Shenzhen Fund for Guangdong Provincial High-Level Clinical Key Specialties(SZGSP014)Sanming Project of Medicine in Shenzhen(SZSM202311012)Shenzhen Science and Technology Planning Project(KCXFZ20211020163813019).
文摘Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its consistency,ease of use,and good quality in extensive clinical practice.In this study,a convolutional neural network(CSPDarknet53)was combined with a transformer to construct a new hybrid model,HCSP-Net.This hybrid model was employed to tri-classify color fundus photography into the normal macula(NM),dry macular degeneration(DMD),and wet macular degeneration(WMD)based on clinical classification manifestations,thus identifying and resolving AMD as early as possible with color fundus photography.To further enhance the performance of this model,grouped convolution was introduced in this study without significantly increasing the number of parameters.HCSP-Net was validated using an independent test set.The average precision of HCSPNet in the diagnosis of AMD was 99.2%,the recall rate was 98.2%,the F1-Score was 98.7%,the PPV(positive predictive value)was 99.2%,and the NPV(negative predictive value)was 99.6%.Moreover,a knowledge distillation approach was also adopted to develop a lightweight student network(SCSP-Net).The experimental results revealed a noteworthy enhancement in the accuracy of SCSP-Net,rising from 94%to 97%,while remarkably reducing the parameter count to a quarter of HCSP-Net.This attribute positions SCSP-Net as a highly suitable candidate for the deployment of resource-constrained devices,which may provide ophthalmologists with an efficient tool for diagnosing AMD.
基金Supported by the Project of Sichuan Medical Association (No.S22058)National Key R&D Project (No.2018YFC1106103).
文摘Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.
基金Supported by Capital Medical University Scientific Research Grant for Undergraduate Students(No.XSKY2023026).
文摘Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.
基金Supported by the Shaanxi Provincial Department of Science and Technology Agency Project(No.2022SF-502)Xi’an Medical University Scientific Research Capacity Improvement Project(No.2022NLTS104)+2 种基金The Fifth Batch of Key Disciplines of Xi’an Medical University(No.medical technology12202306)Yunzhen Optometry Special Fund(No.2021HXZR10)Innovation and Entrepreneurship Training Program for College Students(No.S202211840043).
文摘AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in vivo.METHODS:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB respectively.The MTT assay was utilized to evaluate cell proliferation.Flow cytometry was employed for analysis of cell apoptosis and cell cycle.COL4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by immunofluorescence.The methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by RT-PCR.RESULTS:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 phase.COL4A1 expression was markedly inhibited in UVB treated cells compared to the controls.Hypermethylation status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB exposure.Expressions of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite trend.Results from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure group.CONCLUSION:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.
基金Supported by National Natural Science Foundation of China,No.32200545The GDPH Supporting Fund for Talent Program,No.KJ012020633 and KJ012019530Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine,No.YN2022GK04。
文摘BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.
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 National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
文摘针对从视频中恢复三维人体模型运动序列时,由于图像特征提取能力有限而导致三维人体模型运动序列重建效果不佳的问题,提出了一种基于Involution卷积的三维人体重建方法。首先为了引入自注意力机制,在ResNet50网络结构中加入Involution算子,获取视频图像帧的特征向量,然后使用姿态估计网络和形状估计网络获取人体姿势以及形状参数,最后使用蒙皮多人线性模型(skinned multi-person linear model, SMPL)生成三维人体模型的运动序列。在三维姿态户外数据集(3D pose in the wild, 3DPW)上与视频人体姿态形状估计推理(video inference for body pose and shape estimation, VIBE)方法以及时间一致性网格恢复(temporally consistent mesh recovery, TCMR)方法进行对比实验,平均精度相比于VIBE、TCMR分别提升了3.1%、0.7%,能够为运动捕捉、三维人体动画制作等工作提供更为准确的三维人体模型。
基金supported by NIH/NEI R01 grants (EY031765,EY028100EY024963)+1 种基金BrightFocus Foundation,Research to Prevent Blindness Dolly Green Special Scholar AwardBoston Children’s Hospital Ophthalmology Foundation,Mass Lions Eye Research Fund Inc.(to JC)。
文摘Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.
文摘AIM:To develop and validate a questionnaire to evaluate knowledge,attitude and practice of patients diagnosed with age-related macular degeneration(AMD)who have undergone intravitreal injection treatment.METHODS:This study was conducted among patients diagnosed with AMD in Kuala Lumpur.The generation of the instrument included four phases which included item and domains development,content,face validity and exploratory factor analysis.Content validity and modified Kappa was used for validation of knowledge domain.Exploratory factor analysis was used for validation of both attitude and practice domains.Face validity was conducted in 12 patients,content validity was ascertained in 120 patients and test-retest reliability was determined in 39 patients with AMD.RESULTS:Content validity index(CVI)and modified kappa showed excellent values for most items in the knowledge domain with CVI for item(I-CVI)values between 0.78-1.0 and Kappa values of>0.74.The Kaiser-MeyerOlkin(KMO)sampling adequacy showed acceptable scores of 0.70 and 0.75 for both attitude and practice domains respectively and Bartlett’s Test of sphericity were significant(χ^(2)=0.00,P<0.001).Factor analysis resulted in five factors with thirty items for attitude domain and four factors with twenty items for practice domain.The Cronbach’s alpha showed acceptable values for all items in knowledge,attitude and practice domain with values>0.70 and good test-retest reliability.The final version of the questionnaire consisted of 93 items from four sections consisting of demographic details,knowledge,attitude and practice.CONCLUSION:The findings of this validation and reliability study show that the developed questionnaire has a satisfactory psychometric property for measuring KAP of patients diagnosed with AMD undergoing intravitreal injection treatment.
基金supported by the National Natural Science Foundation of China,Nos.82171138 (to YQZ),82071 062 (to YXC)the Natural Science Foundation of Guangdong Province,No.2021A1515012038 (to YXC)+1 种基金the Fundamental Research Funds for the Central Universities,No.20ykpy91 (to YXC)the Sun Yat-Sen Clinical Research Cultivating Program,No.SYS-Q-201903 (to YXC)。
文摘Patients with age-related hearing loss face hearing difficulties in daily life.The causes of age-related hearing loss are complex and include changes in peripheral hearing,central processing,and cognitive-related abilities.Furthermore,the factors by which aging relates to hearing loss via changes in audito ry processing ability are still unclear.In this cross-sectional study,we evaluated 27 older adults(over 60 years old) with age-related hearing loss,21 older adults(over 60years old) with normal hearing,and 30 younger subjects(18-30 years old) with normal hearing.We used the outcome of the uppe r-threshold test,including the time-compressed thres h old and the speech recognition threshold in noisy conditions,as a behavioral indicator of auditory processing ability.We also used electroencephalogra p hy to identify presbycusis-related abnormalities in the brain while the participants were in a spontaneous resting state.The timecompressed threshold and speech recognition threshold data indicated significant diffe rences among the groups.In patients with age-related hearing loss,information masking(babble noise) had a greater effect than energy masking(speech-shaped noise) on processing difficulties.In terms of resting-state electroencephalography signals,we observed enhanced fro ntal lobe(Brodmann’s area,BA11) activation in the older adults with normal hearing compared with the younger participants with normal hearing,and greater activation in the parietal(BA7) and occipital(BA19) lobes in the individuals with age-related hearing loss compared with the younger adults.Our functional connection analysis suggested that compared with younger people,the older adults with normal hearing exhibited enhanced connections among networks,including the default mode network,sensorimotor network,cingulo-opercular network,occipital network,and frontoparietal network.These results suggest that both normal aging and the development of age-related hearing loss have a negative effect on advanced audito ry processing capabilities and that hearing loss accele rates the decline in speech comprehension,especially in speech competition situations.Older adults with normal hearing may have increased compensatory attentional resource recruitment represented by the to p-down active listening mechanism,while those with age-related hearing loss exhibit decompensation of network connections involving multisensory integration.
文摘Age-related macular degeneration is a major global cause of central visual impairment and seve re vision loss.With an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ctor treatment is likely to increase.In addition,current conventional treatment is only available for the late neovascular stage of age-related macular degeneration,and injections can come with potentially devastating complications,introducing the need for more economical and ris kfree treatment.In recent years,exosomes,which are nano-sized extracellular vesicles of an endocytic origin,have shown immense potential as diagnostic biomarkers and in the therapeutic application,as they are bestowed with characte ristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells.Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases;however,exosomes as a potential therapy for seve ral retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically.This article will focus on the limited literature availa ble on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures,as well as briefly identify future research directions.Current literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury,N-methyl-N-nitrosourea,and royal college of surgeon models,which mimic inflammatory and degenerative aspects of agerelated macular degeneration.These have shown promising results in preserving retinal function and morphology,as well as protecting photoreceptors from apoptosis.Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cyto kines,mRNAs,and proteins involved in photo receptor degeneration pathways to exert a therapeutic effect.Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.
基金Supported by Supporting Fund Project of Shaanxi Provincial Department of Science and Technology Agency Project(No.2022SF-502)Special Scientific Research Program of Education Department of Shaanxi Provincial Government(No.21JK0891)+1 种基金Young Talent Lifting Project of Xi’an Science and Technology Association(No.095920221365)Innovation and Entrepreneurship Training Program for College students of Xi’an Medical University(No.121521113)。
文摘AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.
文摘·AIM:To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor(VEGF)injections to treat neovascular agerelated macular degeneration(n AMD)with subretinal fluid(SRF)and pigment epithelial detachment(PED).·METHODS:This prospective study included eyes with n AMD previously treated with as-needed anti-VEGF injections.The patients were treated with six monthly intravitreal injections of ranibizumab.Quantitative volumetric segmentation analyses of the SRF and PED were performed.The main outcome measures included best-corrected visual acuity(BCVA),and SRF and PED volumes.·RESULTS:Twenty eyes of 20 patients were included in this study.At the 6-month follow-up,BCVA and PED volume did not change significantly(P=0.110 and 0.999,respectively)but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3(P=0.002).The absorption rate of the SRF volume was negatively correlated with the duration of previous antiVEGF treatment(P=0.029).Seven of the 20 eyes(35%)showed a fluid-free macula and significant improvement in BCVA(P=0.036)by month 6.·CONCLUSION:Quantifying the SRF can precisely determine the patient’s responsiveness to anti-VEGF treatment of n AMD.