Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, Plock, Poland.
Acta Ophthalmol. 2024 Nov;102(7):759-772. doi: 10.1111/aos.16744. Epub 2024 Aug 1.
Age-related macular degeneration (AMD) is an emerging cause of blindness in aged people worldwide. One of the key signs of AMD is the degeneration of the retinal pigment epithelium (RPE), which is indispensable for the maintenance of the adjacent photoreceptors. Because of impaired energy metabolism resulting from constant light exposure, hypoxia, and oxidative stress, accumulation of drusen in AMD-affected eyes is observed. Drusen contain damaged cellular proteins, lipoprotein particles, lipids and carbohydrates and they are related to impaired protein clearance, inflammation, and extracellular matrix modification. When autophagy, a major cellular proteostasis pathway, is impaired, the accumulations of intracellular lipofuscin and extracellular drusen are detected. As these aggregates grow over time, they finally cause the disorganisation and destruction of the RPE and photoreceptors leading to visual loss. In this review, the role of autophagy in drusen biogenesis is discussed since impairment in removing cellular waste in RPE cells plays a key role in AMD progression. In the future, means which improve intracellular clearance might be of use in AMD therapy to slow the progression of drusen formation.
年龄相关性黄斑变性（AMD）是全球老年人致盲的一个新兴原因。AMD 的一个关键标志是视网膜色素上皮（RPE）的退化，它对于维持相邻的光感受器是必不可少的。由于持续的光暴露、缺氧和氧化应激导致的能量代谢受损，在 AMD 受影响的眼睛中观察到了玻璃膜疣的积累。玻璃膜疣含有受损的细胞蛋白、脂蛋白颗粒、脂质和碳水化合物，它们与受损的蛋白质清除、炎症和细胞外基质修饰有关。当主要的细胞蛋白稳态途径自噬受损时，会检测到细胞内脂褐素和细胞外玻璃膜疣的积累。随着这些聚集体随时间的推移而生长，它们最终导致 RPE 和光感受器的组织和破坏，导致视力丧失。在这篇综述中，讨论了自噬在玻璃膜疣发生中的作用，因为 RPE 细胞中清除细胞废物的能力受损在 AMD 进展中起着关键作用。在未来，改善细胞内清除的方法可能对 AMD 治疗有用，以减缓玻璃膜疣形成的进展。
