Age-related macular degeneration (AMD) is the major diagnosis for severe and irreversible central loss of vision in elderly people in the developed countries. The loss of vision involves primarily a progressive degeneration and cell death of postmitotic retinal pigment epithelial cells (RPE), which secondarily evokes adverse effects on photoreceptor cells. The RPE cells are exposed to chronic oxidative stress from three sources: their high levels of oxygen consumption, their exposure to the high levels of lipid peroxidation derived from the photoreceptor outer segments and their exposure to constant light stimuli. Cells increase the expression of heat shock proteins (HSPs) in order to normalize their growth conditions in response to various environmental stress factors, e.g. oxidative stress. The HSPs function as molecular chaperones by preventing the accumulation of cellular cytotoxic protein aggregates and assisting in correct folding of both nascent and misfolded proteins. Increased HSPs levels are observed in the retina of AMD patients, evidence of stressed tissue. A hallmark of RPE cell aging is lysosomal lipofuscin accumulation reflecting a weakened capacity to degrade proteins in lysosomes. The presence of lipofuscin increases the misfolding of intracellular proteins, which evokes additional stress in the RPE cells. If the capacity of HSPs to repair protein damages is overwhelmed, then the proteins are mainly cleared in proteasomes or in lysosomes. In this review, we discuss the role of heat shock proteins, proteasomes, and lysosomes and autophagic processes in RPE cell proteolysis and how these might be involved in development of AMD. In addition to classical lysosomal proteolysis, we focus on the increasing evidence that, HSPs, proteasomes and autophagy regulate protein turnover in the RPE cells and thus have important roles in AMD disease.

年龄相关性黄斑变性（AMD）是发达国家老年人严重且不可逆的中心性视力丧失的主要诊断。视力丧失主要涉及有丝分裂后视网膜色素上皮细胞（RPE）的进行性退化和细胞死亡，其次引起对感光细胞的不利影响。RPE细胞暴露于来自三种来源的慢性氧化应激：其高水平的氧气消耗，其暴露于源自感光器外部部分的高水平的脂质过氧化作用以及其暴露于恒定的光刺激下。细胞增加热休克蛋白（HSP）的表达，以响应各种环境应激因素（例如氧化应激）使它们的生长条件正常化。HSP通过阻止细胞细胞毒性蛋白质聚集物的积累并协助新生和错误折叠的蛋白质的正确折叠来充当分子伴侣。在AMD患者的视网膜中观察到HSP水平升高，这是组织受压的证据。RPE细胞衰老的标志是溶酶体脂褐素积累，反映了降解溶酶体中蛋白质的能力减弱。脂褐素的存在增加了细胞内蛋白质的错误折叠，这引起了RPE细胞的额外压力。如果HSP修复蛋白质损伤的能力不堪重负，则蛋白质主要在蛋白酶体或溶酶体中清除。在这篇评论中，我们讨论了热激蛋白，蛋白酶体，RPE细胞蛋白水解中的溶酶体和自噬过程，以及它们可能如何参与AMD的发展。除了经典的溶酶体蛋白水解，我们还将重点放在越来越多的证据上，即HSP，蛋白酶体和自噬调节RPE细胞中的蛋白质更新，因此在AMD疾病中具有重要作用。