Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Invest Ophthalmol Vis Sci. 2024 Oct 1;65(12):20. doi: 10.1167/iovs.65.12.20.
Age-related macular degeneration (AMD) stands as a leading cause of severe visual impairment and blindness among the elderly globally. As a multifactorial disease, AMD's pathogenesis is influenced by genetic, environmental, and age-related factors, with lipid metabolism abnormalities and complement system dysregulation playing critical roles. This review delves into recent advancements in understanding the intricate interaction between these two crucial pathways, highlighting their contribution to the disease's progression through chronic inflammation, drusen formation, and retinal pigment epithelium dysfunction. Importantly, emerging evidence points to dysregulated lipid profiles, particularly alterations in high-density lipoprotein levels, oxidized lipid deposits, and intracellular lipofuscin accumulation, as exacerbating factors that enhance complement activation and subsequently amplify tissue damage in AMD. Furthermore, genetic studies have revealed significant associations between AMD and specific genes involved in lipid transport and complement regulation, shedding light on disease susceptibility and underlying mechanisms. The review further explores the clinical implications of these findings, advocating for a novel therapeutic approach that integrates lipid metabolism modulators with complement inhibitors. By concurrently targeting these pathways, the dual-targeted approach holds promise in significantly improving outcomes for AMD patients, heralding a new horizon in AMD management and treatment.
年龄相关性黄斑变性（AMD）是全球老年人严重视力损害和失明的主要原因。作为一种多因素疾病，AMD 的发病机制受遗传、环境和年龄相关因素的影响，脂质代谢异常和补体系统失调起着关键作用。本综述深入探讨了最近在理解这两个关键途径之间复杂相互作用方面的进展，强调了它们通过慢性炎症、玻璃膜疣形成和视网膜色素上皮功能障碍对疾病进展的贡献。重要的是，新出现的证据表明，脂质谱失调，特别是高密度脂蛋白水平、氧化脂质沉积和细胞内脂褐素积累的改变，是加剧因素，可增强补体激活，并随后放大 AMD 中的组织损伤。此外，遗传研究表明，AMD 与涉及脂质转运和补体调节的特定基因之间存在显著关联，揭示了疾病易感性和潜在机制。该综述进一步探讨了这些发现的临床意义，倡导采用一种新的治疗方法，将脂质代谢调节剂与补体抑制剂相结合。通过同时针对这些途径，双重靶向方法有望显著改善 AMD 患者的预后，为 AMD 的管理和治疗开辟新的前景。
