Kijlstra Aize, Berendschot Tos T J M
University Eye Clinic Maastricht, Maastricht, The Netherlands.
Ophthalmic Res. 2015;54(2):64-73. doi: 10.1159/000432401. Epub 2015 Jul 9.
Age-related macular degeneration (AMD) is a progressive eye disease affecting many elderly individuals. It has a multifactorial pathogenesis and is associated with numerous environmental (e.g. smoking, light and nutrition) and genetic risk factors. A breakthrough in the mechanisms causing AMD is emerging; the involvement of the alternative pathway of the complement system appears to play a pivotal role. This has led to the statement that AMD is a disease caused by a hyperactive complement system, allowing the term 'complementopathy' to define it more precisely. Abundant evidence includes: the identification of drusen components as activators of complement, immunohistochemical data showing the presence of many species of the complement system in the retinal pigment epithelium-Bruch's membrane-choroidocapillary region of AMD eyes, a strong association of AMD with certain genetic complement protein variants, raised complement levels in blood from AMD patients and the preliminary successful treatments of geographic atrophy with complement factor D (FD) inhibitors. FD is the rate-limiting enzyme of the alternative complement pathway, and is produced by adipose tissue. Recent findings suggest that nutrition may play a role in controlling the level of FD in the circulation. Addressing modifiable risk factors such as smoking and nutrition may thus offer opportunities for the prevention of AMD.
年龄相关性黄斑变性（AMD）是一种影响众多老年人的进行性眼病。它具有多因素发病机制，与众多环境因素（如吸烟、光照和营养）以及遗传风险因素相关。导致AMD的机制正在出现突破；补体系统替代途径的参与似乎起着关键作用。这导致了一种说法，即AMD是一种由补体系统过度活跃引起的疾病，使得“补体病”这一术语能更精确地定义它。大量证据包括：将玻璃膜疣成分鉴定为补体激活剂、免疫组化数据显示AMD患者眼睛的视网膜色素上皮 - 布鲁赫膜 - 脉络膜毛细血管区域存在多种补体系统成分、AMD与某些遗传补体蛋白变体的强关联、AMD患者血液中补体水平升高以及使用补体因子D（FD）抑制剂对地图样萎缩进行初步成功治疗。FD是补体替代途径的限速酶，由脂肪组织产生。最近的研究结果表明，营养可能在控制循环中FD的水平方面发挥作用。因此，解决诸如吸烟和营养等可改变的风险因素可能为预防AMD提供机会。
