Nita Małgorzata, Grzybowski Andrzej
Domestic and Specialized Medicine Centre "Dilmed", 40-231 Katowice, Poland.
Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Gorczyczewskiego 2/3, 61-553 Poznań, Poland.
Antioxidants (Basel). 2023 Jun 29;12(7):1368. doi: 10.3390/antiox12071368.
Age-related macular degeneration (AMD), an oxidative stress-linked neurodegenerative disease, leads to irreversible damage of the central retina and severe visual impairment. Advanced age and the long-standing influence of oxidative stress and oxidative cellular damage play crucial roles in AMD etiopathogenesis. Many authors emphasize the role of heterophagy, autophagy, and mitophagy in maintaining homeostasis in the retina. Relevantly modifying the activity of both macroautophagy and mitophagy pathways represents one of the new therapeutic strategies in AMD. Our review provides an overview of the antioxidative roles of heterophagy, autophagy, and mitophagy and presents associations between dysregulations of these molecular mechanisms and AMD etiopathogenesis. The authors performed an extensive analysis of the literature, employing PubMed and Google Scholar, complying with the 2013-2023 period, and using the following keywords: age-related macular degeneration, RPE cells, reactive oxygen species, oxidative stress, heterophagy, autophagy, and mitophagy. Heterophagy, autophagy, and mitophagy play antioxidative roles in the retina; however, they become sluggish and dysregulated with age and contribute to AMD development and progression. In the retina, antioxidative roles also play in RPE cells, NFE2L2 and PGC-1α proteins, NFE2L2/PGC-1α/ARE signaling cascade, Nrf2 factor, p62/SQSTM1/Keap1-Nrf2/ARE pathway, circulating miRNAs, and Yttrium oxide nanoparticles performed experimentally in animal studies.
年龄相关性黄斑变性（AMD）是一种与氧化应激相关的神经退行性疾病，会导致视网膜中央不可逆损伤和严重视力损害。高龄以及氧化应激和氧化细胞损伤的长期影响在AMD的病因发病机制中起关键作用。许多作者强调异噬、自噬和线粒体自噬在维持视网膜内稳态中的作用。相关地调节巨自噬和线粒体自噬途径的活性是AMD新的治疗策略之一。我们的综述概述了异噬、自噬和线粒体自噬的抗氧化作用，并介绍了这些分子机制失调与AMD病因发病机制之间的关联。作者利用PubMed和谷歌学术对2013年至2023年期间的文献进行了广泛分析，使用了以下关键词：年龄相关性黄斑变性、视网膜色素上皮细胞、活性氧、氧化应激、异噬、自噬和线粒体自噬。异噬、自噬和线粒体自噬在视网膜中发挥抗氧化作用；然而，它们会随着年龄增长而变得迟缓且失调，促进AMD的发生和发展。在视网膜中，视网膜色素上皮细胞、NFE2L2和PGC-1α蛋白、NFE2L2/PGC-1α/ARE信号级联、Nrf2因子、p62/SQSTM1/Keap1-Nrf2/ARE途径、循环微小RNA以及动物实验中进行的氧化钇纳米颗粒也发挥抗氧化作用。
