Eye Center of Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
Hunan Key Laboratory of Ophthalmology, Central South University, 410008, Changsha, China.
Signal Transduct Target Ther. 2023 Sep 15;8(1):352. doi: 10.1038/s41392-023-01570-w.
The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or "proteostasis". The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1. ER stress is multifaceted, and acts on aspects at the epigenetic level, including transcription and protein processing. Accumulated data indicates its key role in protein homeostasis and other diverse functions involved in various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, ocular surface diseases, and myopia. This review summarizes the molecular mechanisms underlying the aforementioned ocular diseases from an ER stress perspective. Drugs (chemicals, neurotrophic factors, and nanoparticles), gene therapy, and stem cell therapy are used to treat ocular diseases by alleviating ER stress. We delineate the advancement of therapy targeting ER stress to provide new treatment strategies for ocular diseases.
内质网（ER）是蛋白质动态平衡或“蛋白稳态”的质量控制细胞器。蛋白质质量控制系统包括 ER 相关降解、蛋白伴侣和自噬。当内质网中错误折叠和未折叠蛋白质的积累破坏蛋白稳态时，内质网应激就会被激活。内质网应激通过启动蛋白激酶 R 样内质网激酶、激活转录因子 6 和需要肌醇的酶 1，激活适应性未折叠蛋白反应来恢复蛋白稳态。内质网应激是多方面的，作用于表观遗传水平的各个方面，包括转录和蛋白质加工。大量数据表明，它在蛋白质动态平衡和其他涉及各种眼部疾病的多种功能中起着关键作用，如青光眼、糖尿病视网膜病变、年龄相关性黄斑变性、视网膜色素变性、色盲、白内障、眼部肿瘤、眼表疾病和近视。这篇综述从内质网应激的角度总结了上述眼部疾病的分子机制。药物（化学物质、神经营养因子和纳米颗粒）、基因治疗和干细胞治疗通过缓解内质网应激来治疗眼部疾病。我们描述了靶向内质网应激的治疗方法的进展，为眼部疾病提供了新的治疗策略。
