内质网应激在年龄相关性黄斑变性中的研究进展  

Endoplasmic reticulum stress in the pathogenesis of age-related macular degeneration

作　　者：刘霞[1] 王艳[1] 江华维 任玉玲[1] 陈晨[1] Xia Liu;Yan Wang;Hua-Wei Jiang;Yu-Ling Ren;Chen Chen(Department of Ophthalmology, Fourth Affiliated Hospital of Kunming Medical University, Department of Ophthalmology, the Second People's Hospital of Yunnan Province, Yunnan Eye Institute, The Ocular Disease and Clinical Medicine Research Center of Yunnan Province, The Ocular Disease Clinical Medicine Center of Yunnan Province, Key Laboratory of Yunnan Province for the Prevention and Treatment of Ophthalmology, Expert Workstation of Yao Ke, Kunming 650021, Yunnan Province, China)

机构地区：[1]昆明医科大学第四附属医院眼科云南省第二人民医院眼科云南省眼科研究所云南省眼部疾病临床医学研究中心云南省眼病临床医学中心云南省眼科疾病防治研究重点实验室云南省姚克专家工作站,中国云南省昆明市650021

出　　处：《国际眼科杂志》2022年第2期244-248,共5页International Eye Science

基　　金：国家自然科学基金项目(No.81660167);云南省卫生健康委员会医学后备人才培养计划(No.H-2019057)。

摘　　要：年龄相关性黄斑变性(ARMD)是老年人不可逆视力损害的主要原因,以黄斑区玻璃膜疣的形成、色素紊乱、地图样萎缩、脉络膜新生血管形成为主要病理特征,视网膜色素上皮(RPE)细胞功能失调与ARMD关系密切。内质网是真核生物一个特殊的细胞器,主要负责蛋白的合成、修饰、整合和质量控制,并参与Ca^(2+)稳态维持和脂质的生物合成。细胞内外环境的变化,导致内质网应激,激活细胞内的信号转导通路——未折叠蛋白反应,以恢复细胞功能和维持细胞内环境稳态。但长期强烈的内质网应激可能导致内质网动态平衡难以恢复,而触发细胞凋亡。ARMD的发病机制尚未完全阐明,但大量研究证明内质网应激与其相关。本文就内质网应激的信号转导通路、内质网应激在RPE中的生理作用及内质网应激可能介导ARMD的机制作一综述。Age-related macular degeneration(ARMD)is a main cause of irreversible visual impairment in the elderly.The major pathological features are drusen formation,macular pigment disorder,geographic atrophy and abnormal neovascularization.Retinal pigment epithelium(RPE)function is impaired in ARMD.Endoplasmic reticulum(ER)is an organelle in eukaryotes responsible for protein synthesis,modification,integration and quality control.ER also participates in the maintenance of calcium homeostasis and lipid biosynthesis.Stimuli from the external and internal environment may trigger ER stress and therefore activate the intracellular signal transduction pathway-the unfolded protein response(UPR),to restore cell homeostasis.However,prolonged ER stress may lead to apoptosis.The pathogenesis of ARMD has not been fully elucidated,nevertheless,compelling evidence demonstrates that ER stress is involved.In this article,we summarize recent advances in UPR pathways,as well as the role of ER stress in the physiological function of RPE and in the pathogenesis of ARMD.

关 键 词：年龄相关性黄斑变性 内质网应激 未折叠蛋白反应 视网膜色素上皮细胞 细胞凋亡 

分 类 号：R73[医药卫生—肿瘤]