线粒体遗传学机制在年龄相关性黄斑变性中的研究进展

Research progress of mitochondrial genetics in age-related macular degeneration

线粒体是细胞的"能量工厂", 其功能受细胞核及线粒体双重遗传学机制严格调控。随着年龄增加, 线粒体基因组复制错误及氧化损伤积累、表观修饰模式改变, 造成衰老相关线粒体功能障碍。上述机制在年龄相关性黄斑变性(AMD)的发生和发展中发挥着重要作用。衰老相关线粒体遗传物质改变发生于视网膜色素上皮(RPE)及神经视网膜细胞中, 影响细胞能量代谢及功能活性, 介导RPE氧化应激、溶酶体损伤及炎性凋亡等多个病理过程, 并最终导致RPE功能障碍、视网膜沉积物及炎症微环境形成。针对线粒体遗传学的保护性干预是AMD早期预防和治疗的新思路, 线粒体衍生肽Humanin等新靶点正在被广泛研究。本文对线粒体遗传学机制与AMD疾病进展相关研究进行综述, 为探讨AMD的病理机制和防治策略提供新的思路。

Mitochondria are the center of cellular energy metabolism,and their functions are tightly regulated by the nuclear and mitochondria genomes.Potential mechanisms responsible for age-related mitochondrial dysfunction include the accumulation of mitochondrial DNA(mtDNA)damage caused by replication errors or oxidative damage,and the epigenetic changes in mtDNA(mitoepigenetics).These mechanisms are essential for the development and progression of age-related macular degeneration(AMD).Age-related mtDNA damage disrupts energy metabolism and cellular function in the retinal pigment epithelium(RPE)and neuroretinal cells,which further mediates oxidative stress,lysosomal dysfunction and pyroptosis,resulting in RPE degeneration,drusen deposition and retinal inflammation.Mitochondrial genome protection,such as humanin administration,may be a promising preventive or therapeutic target in the early stages of AMD.This review focused on the research progress of the mitochondrial genetic mechanism in AMD pathogenesis and provided new ideas for exploring the prevention and treatment strategies of AMD.