内质网应激：分子机制和治疗靶点,Signal Transduction and Targeted Therapy

内质网 (ER) 作为蛋白质稳态或“蛋白质稳态”的质量控制细胞器。蛋白质质量控​​制系统涉及内质网相关降解、蛋白质伴侣和自噬。当内质网中错误折叠和未折叠蛋白质的积累导致蛋白质稳态被破坏时，内质网应激就会被激活。ER 应激通过启动蛋白激酶 R 样 ER 激酶、激活转录因子 6 和需要酶 1 的肌醇，激活适应性未折叠蛋白反应以恢复蛋白质稳态。 ER 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。积累的数据表明，其在蛋白质稳态和涉及各种眼部疾病的其他多种功能中发挥关键作用，例如青光眼、糖尿病性视网膜病变、年龄相关性黄斑变性、色素性视网膜炎、全色盲、白内障、眼部肿瘤、眼表疾病和近视。本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）、基因疗法和干细胞疗法用于通过减轻内质网应激来治疗眼部疾病。我们描绘了针对内质网应激的治疗进展，为眼部疾病提供新的治疗策略。

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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.