Department of Ophthalmology; Institute of Clinical Medicine; University of Eastern Finland; Kuopio, Finland; Department of Ophthalmology; Kuopio University Hospital; Kuopio, Finland.
Autophagy. 2013 Jul;9(7):973-84. doi: 10.4161/auto.24546. Epub 2013 Apr 9.
Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD.
年龄相关性黄斑变性(AMD)是一种复杂的、退行性的和进行性的眼部疾病,通常不会导致完全失明,但可能导致严重的中心视力丧失。AMD 的危险因素包括年龄、遗传、饮食、吸烟、氧化应激和许多与心血管相关的危险因素。自噬是一种细胞内的管家过程,它可以清除受损的细胞器和蛋白聚集体,而在视网膜色素上皮(RPE)中,异噬作用是对外源性光感受器外节的吞噬作用。大量研究表明,自噬和异噬在 RPE 中都非常活跃。迄今为止,越来越多的证据表明,持续的氧化应激会损害自噬和异噬作用,增加蛋白聚集,并导致炎症小体激活,从而导致 AMD 的病理表型。本综述将这些关键的病理主题联系在一起,并探讨了自噬作为 AMD 潜在治疗靶点的可能性。
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