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The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration
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作者 Qianzi Jin Suyu Wang +2 位作者 Yujia Yao Qin Jiang Keran Li 《Neural Regeneration Research》 SCIE CAS 2025年第10期2741-2757,共17页
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are... Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms. 展开更多
关键词 age-related macular degeneration biological agents blinding eye disease dietary nutrition fecal microbial transplantation gut-eye axis intestinal flora METABOLITE MICROECOLOGY neurodegenerative disease
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Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration
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作者 Blanca Molins Andrea Rodríguez +1 位作者 Víctor Llorenç Alfredo Adán 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第12期2626-2636,共11页
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
关键词 age-related macular degeneration Bruch's membrane DECELLULARIZATION retinal pigment epithelium SCAFFOLD
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Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets
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作者 Jingxiang Zhang Xia Sheng +3 位作者 Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang 《Neural Regeneration Research》 SCIE CAS 2025年第2期378-393,共16页
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
关键词 choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition MYOFIBROBLAST neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor
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NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications
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作者 Xiao-Li Wang Yun-Xia Gao +1 位作者 Qiong-Zhen Yuan Ming Zhang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第8期1531-1544,共14页
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
关键词 AUTOPHAGY age-related macular degeneration NLRP3 inflammasome retinal degeneration retinal ganglion cells
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Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis
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作者 Zi-Ling Hu Yu-Xuan Wang +4 位作者 Zi-Yue Lin Wen-Shuo Ren Bo Liu Hui Zhao Qiong Qin 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第7期1344-1362,共19页
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
关键词 NRF2 upstream regulators retinal pigment epithelia age-related macular degeneration oxidative stress
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HCSP-Net:A Novel Model of Age-Related Macular Degeneration Classification Based on Color Fundus Photography
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作者 Cheng Wan Jiani Zhao +2 位作者 Xiangqian Hong Weihua Yang Shaochong Zhang 《Computers, Materials & Continua》 SCIE EI 2024年第4期391-407,共17页
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
关键词 Computer-aided diagnosis deep learning age-related macular degeneration TRANSFORMER
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Investigating the causal link between gut microbiota and dry age-related macular degeneration:a bidirectional Mendelian randomization study
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作者 Hai-Yan Huang Jing Wang +1 位作者 Bo Qin Yao Tan 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第9期1723-1730,共8页
AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study... AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism. 展开更多
关键词 dry age-related macular degeneration gut microbiota mendelian randomization gut-retina axis genome-wide association study
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Comparative study between swept-source and spectraldomain OCTA for imaging of choroidal neovascularization in age-related macular degeneration
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作者 Ji-Xian Ma Zhuo-Yi Zhang +7 位作者 Rong Di Jia-Jie Yang Si-Wen Tian Ya-Zhou Qin Wan-Hu Zhang Jian-Qin Lei Qiu-Ping Liu Jing-Ming Li 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第11期2067-2073,共7页
AIM:To compare the dif ferences of choroidal neovascularization(CNV)measurements between sweptsource and spectral-domain optical coherence tomography angiography(SS-OCTA and SD-OCTA)in neovascular agerelated macular d... AIM:To compare the dif ferences of choroidal neovascularization(CNV)measurements between sweptsource and spectral-domain optical coherence tomography angiography(SS-OCTA and SD-OCTA)in neovascular agerelated macular degeneration(nAMD)and the imaging reliability of the two devices.METHODS:Prospective comparative study.SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm2 centered on the neovascularization.Only qualified images were chosen and the border of CNV was manually delineated by two graders independently.The area of CNV(ACNV),vascular perfusion density(PD),and vessel length density(VLD)within the delineation were calculated using Image J.The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis.The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient(ICC).RESULTS:A total of 18 patients(22 eyes)with nAMD were included.The measurements of ACNV,PD,and VLD were 7.247±4.586 and 4.901±3.741 mm^(2),43.202±9.636 and 34.904±10.489,6.339±1.228 and 5.908±1.741 mm^(-1) for SS-OCTA and SD-OCTA,respectively.The differences between the two devices were 2.346±3.030 mm^(2)(Z=-3.782,P<0.0001),8.298±14.160(Z=-2.419,P=0.016),and 0.431±2.114 mm^(-1)(Z=-0.828,P=0.408)for ACNV,PD and VLD,respectively.The ICC between two graders were 0.893(P<0.001),0.902(P<0.001),0.885(P<0.001)for ACNV,PD,VLD in SS-OCTA,and 0.971(P<0.001),0.976(P<0.001),0.973(P<0.001)in SD-OCTA,respectively.CONCLUSION:Both OCTA devices have high imaging reliability.Compared with SD-OCTA,SS-OCTA has a larger ACNV measurements,but doesn’t show better resolution of internal vessels of CNV and well signal strength. 展开更多
关键词 neovascular age-related macular degeneration swept-source SPECTRAL-DOMAIN optical coherence tomography angiography
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RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration
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作者 Miao Xu Yan Gao +2 位作者 Wenjie Yin Qinghuai Liu Songtao Yuan 《Journal of Biomedical Research》 CAS CSCD 2024年第5期500-511,I0012-I0018,共19页
The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have bee... The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD. 展开更多
关键词 age-related macular degeneration retinal pigment epithelium high-throughput RNA-sequencing bioinformatics analysis
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Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration:An observational study
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作者 Zhen-Huan Huang Xue-Zhao Tu +3 位作者 Qi Lin Mei Tu Guo-Cai Lin Kai-Ping Zhang 《World Journal of Radiology》 2024年第9期418-428,共11页
BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential fo... BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning. 展开更多
关键词 Vascular endothelial growth factor Macular degeneration NEOVASCULARIZATION age-related macular degeneration Choroidal neovascularization Optical coherence tomography angiography NOMOGRAM
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Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration 被引量:3
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作者 Meenakshi Maurya Kiran Bora +4 位作者 Alexandra K.Blomfield Madeline C.Pavlovich Shuo Huang Chi-Hsiu Liu Jing Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第10期2173-2181,共9页
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
关键词 age-related macular degeneration ANTIOXIDANT nuclear factor erythroid-2-related factor 2 oxidative stress retinal pigment epithelium REV-ERBα
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Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration 被引量:2
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作者 Bo Hee Kim In Boem Chang +1 位作者 Hyeong Gon Yu In Hwan Hong 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第6期909-914,共6页
·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
关键词 neovascular age-related macular degeneration anti-vascular endothelial growth factor treatment drug tolerance persistent subretinal fluid volumetric fluid analysis
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Extracellular vesicles as a potential therapeutic for age-related macular degeneration 被引量:1
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作者 Lorraine L.C.Chow Ben Mead 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期1876-1880,共5页
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
关键词 age-related macular degeneration EXOSOMES extracellular vesicles MIRNA NEUROPROTECTION PHOTORECEPTORS RETINA retinal pigment epithelium
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Development of Knowledge,Attitude and Practice Questionnaire for age-related macular degeneration patients 被引量:1
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作者 Mohd Harimi Abd Rahman Prashanti Amirtharatnam +3 位作者 Sharanjeet Sharanjeet-Kaur Sumithira Narayanasamy Hanif Farhan Mohd Rasdi Mae-Lynn Catherine Bastion 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第4期589-600,共12页
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
关键词 KNOWLEDGE ATTITUDES PRACTICE age-related macular degeneration instrument development
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Retinal pigment epithelium–Bruch’s membrane volume in grading of age-related macular degeneration 被引量:1
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作者 Fabian Kananen Ilkka Immonen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第11期1827-1831,共5页
AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)gradin... AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum. 展开更多
关键词 age-related macular degeneration DRUSEN optical coherence tomography Bruch’s membrane
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Implication of gut microbiome in age-related macular degeneration 被引量:1
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作者 Wendy Luo Dimitra Skondra 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第12期2699-2700,共2页
Age-related macular degeneration(AMD) is the most common cause of blindness in the United States in adults over 55 years of age and is one of the leading global causes of blindness: at least 196 million of the worldwi... Age-related macular degeneration(AMD) is the most common cause of blindness in the United States in adults over 55 years of age and is one of the leading global causes of blindness: at least 196 million of the worldwide population have AMD, and prevalence is projected to rise to 288 million by 2040(Lin et al., 2021). As cases and disease burden increase, improvements in the characterization of AMD pathobiology and exploration of potential therapeutic solutions are necessary first steps in addressing this global health concern. 展开更多
关键词 degeneration AMD STEPS
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Circular RNA expression and the competitive endogenous RNA network in pathological,age-related macular degeneration events:A cross-platform normalization study
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作者 Ruxu Sun Hongjing Zhu +7 位作者 Ying Wang Jianan Wang Chao Jiang Qiuchen Cao Yeran Zhang Yichen Zhang Songtao Yuan Qinghuai Liu 《The Journal of Biomedical Research》 CAS CSCD 2023年第5期367-381,共15页
Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used t... Age-related macular degeneration(AMD)causes irreversible blindness in people aged over 50 worldwide.The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD.In the current study,we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database.We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis.Peroxisome and tumor necrosis factor-α(TNF-α)signaling and nuclear factor kappa B(NF-κB)were among the top 10 pathways,and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs(circRNAs).We then constructed a competing endogenous RNA network,which is related to differentially expressed circRNAs.This network included seven circRNAs,15 microRNAs,and 82 mRNAs.The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1(HIF-1)signaling pathway was a common downstream event.The results of the current study may provide insights into the pathological processes of atrophic AMD. 展开更多
关键词 age-related macular degeneration retinal pigment epithelium circular RNA bioinformatics analysis competing endogenous RNA
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Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model
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作者 Yun YUAN Wen KONG +1 位作者 Xiao-mei LIU Guo-hua SHI 《Current Medical Science》 SCIE CAS 2023年第2期384-392,共9页
Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate ... Objective Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encodingβ-catenin to treat AMD in a mouse model.Methods Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,andβ-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function ofβ-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results AAV2/8-Y733F-VMD2-β-catenin induced the expression ofβ-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bcl-2.Conclusion AAV2/8-Y733F-VMD2-β-catenin increasedβ-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment. 展开更多
关键词 gene therapy adeno-associated virus age-related macular degeneration retinal pigment epithelium cells Β-CATENIN
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Vision rehabilitation using microperimetric biofeedback training in age-related macular degeneration
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作者 Sri Hudaya Widihastha Erwin Iskandar +3 位作者 Karmelita Satari Irawati Irfani Rova Virgana Primawita Oktarima Amiruddin 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2023年第6期933-938,共6页
·AIM: To determine the impact of microperimetric biofeedback training(MBFT) on the quality of vision in patients with age-related macular degeneration(AMD).·METHODS: This study was a prospective, interventio... ·AIM: To determine the impact of microperimetric biofeedback training(MBFT) on the quality of vision in patients with age-related macular degeneration(AMD).·METHODS: This study was a prospective, interventional, comparative study with subjects of patients diagnosed with AMD in the National Eye Center Cicendo Eye Hospital, Indonesia. Patients were randomly divided into two groups, intervention and non-intervention with 18 patients in each group. The intervention group would receive six MBFT training sessions of 10-minute time duration each.·RESULTS: A statistically significant improvement of best corrected visual acuity(BCVA) was found after the intervention, from 1.24±0.416 to 0.83±0.242(log MAR;P<0.001). A statistically significant improvement for near vision acuity(NVA) was also observed, from 1.02±0.307 log MAR to 0.69±0.278 log MAR(P<0.001). In addition, reading rate increased, from 40.83±30.411 to 65.06±31.598 words/min(P<0.001). Similarly, a comparison of changes in BCVA, NVA, and reading rate between intervention and non-intervention groups showed a significant difference(P<0.001).·CONCLUSION: MBFT significantly and positively impacts visual acuity, NVA, and reading rate in patients with AMD. 展开更多
关键词 microperimetric biofeedback training agerelated macular degeneration vision rehabilitation
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Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy
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作者 Samuel Abokyi Dennis Yan-yin Tse 《Neural Regeneration Research》 SCIE CAS 2025年第2期366-377,共12页
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
关键词 age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma NEUROMODULATION PHAGOCYTOSIS photoreceptor outer segment degradation retinal aging transcription factor EB
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