自噬溶酶体途径缺陷与糖尿病性眼表病变关系的研究进展  

Research progress of autophagy-lysosomal pathway dysfunction in ocular surface diseases associated with diabetes mellitus

作　　者：王亚尼(综述) 周庆军 谢立信(审校) Wang Yani;Zhou Qingjun;Xie Lixin(Eye Institute of Shandong First Medical University,State Key Laboratory Cultivation Base,Shandong Key Laboratory of Eye Diseases,School of Ophthalmology,Shandong First Medical University,Qingdao 266071,China)

机构地区：[1]山东第一医科大学附属眼科研究所,山东省眼部疾病重点实验室-省部共建国家重点实验室培育基地,山东第一医科大学眼科学院,青岛266071

出　　处：《中华实验眼科杂志》2025年第3期283-288,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：山东省第一医科大学学术提升计划(2019ZL001)。

摘　　要：自噬溶酶体途径(ALP)是维持细胞内稳态,清除细胞内未折叠的蛋白质、受损细胞器的重要降解系统,自噬过程主要包括自噬体形成、自噬体与溶酶体融合、自噬底物在成熟溶酶体内降解。干眼、睑板腺功能障碍、角膜病变是常见的糖尿病眼表并发症,临床表现为眼睛干涩、泪液分泌减少、角膜上皮延迟愈合、神经病变(角膜敏感性降低)及内皮功能障碍。糖尿病条件下晚期糖基化终末产物蓄积及活性氧的过量产生引起异常基因表达、氧化应激、炎症反应是糖尿病性眼表病变的重要发病机制。这些发病机制均涉及自噬调控基因缺陷、自噬相关蛋白表达异常及多条自噬信号通路的调控,引起自噬体-溶酶体融合障碍、自噬底物累积及溶酶体功能异常等ALP缺陷,进一步加重氧化应激及炎症因子的释放。糖尿病性眼表病变的发生和发展与ALP缺陷密切相关。本文就ALP缺陷与糖尿病性眼表病变关系的基础研究现状展开综述,以期为研究糖尿病性眼表病变的发病机制和临床治疗提供新的思路。Autophagy-lysosomal pathway(ALP)is the degradation system that remove unfolded proteins and damaged organelles in cells,and plays an important role in maintaining intracellular homeostasis.The process of autophagy mainly includes autophagosome formation,autophagosome-lysosome fusion,and degradation of cargoes in mature lysosomes by lysosomal enzymes.Dry eye disease,meibomian gland dysfunction and keratopathy are common ocular surface diseases associated with diabetes mellitus,and clinical manifestations include dry eyes,reduced tear secretion,persistent corneal epithelial defects,neuropathy(decreased corneal sensitivity)and endothelial cell dysfunction.Aberrant expression of gene,oxidative stress and inflammation related advanced glycosylation end products and reactive oxygen species are significant pathogenesis of ocular surface diseases related to diabetes.Moreover,the above pathogenesis involves defects of autophagy regulatory gene,abnormal expression of autophagy related protein and activation of autophagy signaling pathway which lead to the defects of ALP such as autophagosome lysosome fusion disorder,accumulation of cargoes and abnormal lysosomal function,and the deficiency of autophagy further promoting the oxidative stress and release of inflammatory factors.The occurrence and development of ocular surface diseases associated with diabetes are closely related to the defects of ALP.This article reviews the basic research status between the defects of ALP and diabetic ocular surface diseases to provide new ideas for the mechanism and treatment research.

关 键 词：糖尿病/并发症 眼表疾病 自噬溶酶体途径 氧化应激 晚期糖基化终末产物 

分 类 号：R58[医药卫生—内分泌]