Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
Int J Mol Sci. 2020 Oct 1;21(19):7279. doi: 10.3390/ijms21197279.
Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD's role as a therapeutic new target for future AMD treatment.
年龄相关性黄斑变性（AMD）是老年人严重视力丧失的主要原因。AMD 患者饱受进行性中心模糊/视力丧失的折磨，迄今为止，治疗选择有限。导致视网膜色素上皮（RPE）细胞损伤的 玻璃膜疣积聚是 AMD 发病机制的标志，其中氧化应激和炎症是众所周知的分子机制。然而，当 RPE 暴露于玻璃膜疣时如何做出反应的潜在机制仍知之甚少。程序性细胞死亡（PCD）在细胞对压力的反应和对体内平衡和疾病的调节中起着重要作用。除了经典的细胞凋亡外，最近的研究还发现了新的 PCD 途径，如细胞焦亡、坏死性凋亡和铁死亡，它们可能导致 AMD 中的 RPE 细胞死亡。这些证据可能为 AMD 提供新的治疗靶点。在这篇综述中，我们总结和分析了新型 PCD 与 AMD 之间的关联的最新进展，提出 PCD 作为未来 AMD 治疗的治疗新靶点的作用。
