综述
ENGLISH ABSTRACT
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
王亚尼
周庆军 [综述]
谢立信 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20210111-00025
Research progress of autophagy-lysosomal pathway dysfunction in ocular surface diseases associated with diabetes mellitus
Wang Yani
Zhou Qingjun
Xie Lixin
Authors Info & Affiliations
Wang Yani
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
Zhou Qingjun
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
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
·
DOI: 10.3760/cma.j.cn115989-20210111-00025
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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。

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
ABSTRACT

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.

Diabetes mellitus, complications;Ocular surface disease;Autophagy-lysosomal pathway;Oxidative stress;Advanced glycation end products
Xie Lixin, Email: mocdef.labiamtoheix_nixil
引用本文

王亚尼,周庆军,谢立信. 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[J]. 中华实验眼科杂志,2025,43(03):283-288.

DOI:10.3760/cma.j.cn115989-20210111-00025

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糖尿病是多病因引起的以胰岛素抵抗或胰岛B细胞功能受损、血液中葡萄糖含量增高为特点的慢性代谢性疾病。糖尿病及其并发症给人类健康和社会经济带来严重负担,其患病率在全球呈指数增长,预计2045年糖尿病患者将达6.93亿 [ 1 ]。自噬是细胞的一种自我保护机制,其中自噬溶酶体途径(autophagy lysosome pathway,ALP)是细胞内清除未折叠蛋白质及受损细胞器的降解系统,其功能正常发挥对细胞内稳态起重要的调控作用。许多代谢紊乱性疾病包括肥胖、糖尿病、动脉粥样硬化及神经退行性疾病等均已证实与ALP稳态的缺陷有关 [ 2 ]。高血糖会引起肾脏、眼睛、心血管系统等全身各个器官组织发生一系列严重并发症 [ 3 , 4 , 5 ]。研究证实ALP缺陷参与糖尿病肾病、糖尿病视网膜病变(diabetic retinopathy,DR)等并发症的发病机制 [ 6 , 7 ]。糖尿病性眼表病变包括干眼、睑板腺功能障碍(meibomian gland dysfunction,MGD)、糖尿病性角膜病变 [ 8 ]。目前在糖尿病干眼、角膜创伤愈合及糖尿病角膜神经病变等方面已涉及ALP缺陷。本文就ALP缺陷与糖尿病性眼表病变关系的研究现状展开综述,以增加对糖尿病性眼表疾病发病机制的认识及理解。
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A
谢立信,Email: mocdef.labiamtoheix_nixil
B
所有作者均声明不存在利益冲突
C
山东省第一医科大学学术提升计划 (2019ZL001)
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