Department of Pharmacology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Curr Pharm Des. 2019;25(28):3057-3073. doi: 10.2174/1381612825666190829151314.
Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.
视神经病变是指由缺血、炎症、创伤、肿瘤、线粒体功能障碍、毒素、营养缺乏、遗传等任何原因引起的视神经纤维功能障碍或变性。中枢神经系统神经元在出生后，其轴突的生长能力有限，无论是创伤还是疾病，都会导致不可逆转的视力丧失。近年来，越来越多的实验室证据评估了视神经损伤，重点关注涉及视网膜神经节细胞（RGC）死亡的分子信号通路。营养因子剥夺（TFD）、炎症、氧化应激、线粒体功能障碍、谷氨酸诱导的兴奋性毒性、缺血、缺氧等已被认为是导致 RGC 凋亡的重要分子机制。了解这些障碍为寻找对抗视网膜细胞损伤的新策略提供了更好的视角。褪黑素作为一种广谱抗氧化剂和强大的自由基清除剂，具有保护 RGC 或其他细胞免受各种有害条件（如氧化/硝化应激、缺氧/缺血、炎症过程和细胞凋亡）的能力。在这篇综述中，我们主要强调了涉及 RGC 存活/死亡的分子再生和退化机制，然后总结了褪黑素在一些眼部疾病（包括视神经病变）中 RGC 死亡过程中的可能保护作用。基于本综述提供的信息，褪黑素可能作为一种有前途的药物，减少各种视网膜病理条件下的 RGC 死亡。
