Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.

中文翻译：

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干性 AMD 中的自噬：视网膜色素上皮细胞损伤的一种有前途的治疗策略

干性年龄相关性黄斑变性（AMD）是一种常见的临床疾病，会导致中央视力永久性损伤，并对患者的视力健康构成重大威胁。尽管干性 AMD 的发病机制尚不清楚，但对于视网膜色素上皮 (RPE) 损伤的作用已达成共识。氧化应激和慢性炎症是 RPE 细胞损伤的主要原因，NOD 样受体热蛋白结构域相关蛋白 3 (NLRP3) 炎症小体介导炎症反应，导致 RPE 细胞凋亡。此外，脂褐素积累会导致氧化应激、NLRP3 激活和卵黄样病变（干性 AMD 的标志）的发展，所有这些都可能导致 RPE 功能障碍。自噬过程涉及积累的蛋白质和死细胞的封装、识别和转运至溶酶体进行降解，被认为是细胞自我保护和体内平衡维持的重要途径。最近，RPE细胞自噬被发现与黄斑变性的发展密切相关，使自噬成为干性AMD领域的前沿研究领域。在这篇综述中，我们概述了脂褐素、氧化应激和 NLRP3 炎性体如何通过各自的因果机制损害 RPE。我们总结了自噬、氧化应激和 NLRP3 炎症细胞因子之间的联系。我们的研究结果表明，靶向自噬可以改善 RPE 功能并维持视觉健康，为理解干性 AMD 的发病机制和临床治疗提供新的视角。