Age-Related Macular Degeneration (AMD) is a complex multifactorial disease characterized in its early stages by lipoprotein accumulations in Bruch's Membrane (BrM), seen on fundoscopic exam as drusen, and in its late forms by neovascularization (“wet”) or geographic atrophy of the Retinal Pigmented Epithelial (RPE) cell layer (“dry”). Genetic studies have strongly supported a relationship between the alternative complement cascade, in particular the common H402 variant in Complement Factor H (CFH) and development of AMD. However, the functional significance of the CFH Y402H polymorphism remains elusive. In this article, we critically review the literature surrounding the functional significance of this polymorphism. Furthermore, based on our group's studies we propose a model in which CFH H402 affects CFH binding to heparan sulfate proteoglycans leading to accelerated lipoprotein accumulation in BrM and drusen progression. We also review the literature on the role of other complement components in AMD pathobiologies, including C3a, C5a and the membrane attack complex (MAC), and on transgenic mouse models developed to interrogate in vivo the effects of the CFH Y402H polymorphism.

年龄相关性黄斑变性（AMD）是一种复杂的多因素疾病，其特征是早期以布鲁赫膜（BrM）的脂蛋白积聚为特征，在眼底镜检查中被视为玻璃疣，而后期则以新血管形成（“湿”）或地理萎缩为特征。视网膜色素上皮（RPE）细胞层（“干”）。遗传学研究强烈支持替代补体级联反应，特别是补体因子H（CFH）中常见的H402变异与AMD的发展之间的关系。但是，CFH Y402H多态性的功能意义仍然难以捉摸。在本文中，我们严格地审查了有关该多态性功能意义的文献。此外，基于我们的团队” 在研究中，我们提出了一个模型，其中CFH H402影响CFH与硫酸乙酰肝素蛋白聚糖的结合，从而导致BrM中脂蛋白的积累加速和玻璃疣的发展。我们还回顾了有关其他补体成分在AMD病理学中的作用的文献，包括C3a，C5a和膜攻击复合物（MAC），以及开发用于询问的转基因小鼠模型体内CFH Y402H多态性的影响。