补体疗法在年龄相关性黄斑变性所致地图状萎缩中的治疗进展

Progress of complement therapy for geographic atrophy secondary to age-related macular degeneration

关键词:  年龄相关性黄斑变性  地图状萎缩  补体  治疗进展

Key words:  age-related macular degeneration  geographic atrophy  complement  treatment progress

摘要:

年龄相关性黄斑变性(age-related macular degeneration, AMD)所致地图状萎缩(geographic atrophy, GA)目前仍缺乏有效的治疗方法。越来越多的证据表明，AMD所致GA的发生和发展与补体级联失调密切相关。作为先天性免疫系统的一部分，补体系统在维持人体内环境稳态中起到了重要作用，补体过度激活将打破这一平衡，促进年龄相关性黄斑变性的进展。基于此，针对补体激活途径的潜在靶点包括C1q、C3、C5、CFB、CFD、CFH、CFI和膜攻击复合物，依据药物形式又可分为生物大分子药物、化学小分子药物及基因治疗药物。目前已有多种治疗AMD所致GA的药物进入临床试验，本文总结了GA的补体疗法的临床试验进展，以评估其安全性和有效性。

Abstract:

Geographic atrophy(GA) secondary to age-related macular degeneration(AMD) lacks effective treatment at present. There is growing evidence that the onset and progression of AMD-induced GA is closely related to complement cascade dysregulation. As part of the innate immune system, the complement system plays an important role in maintaining homeostasis in the human body, and overactivation of complement will disrupt this balance and promote the progression of age-related macular degeneration. Based on this finding, C1q, C3, C5, complement factors B, D, H, I and membrane attack complex can be the potential targets for complement activation pathways; and the corresponding drug forms will be biological macromolecules, chemical small molecules and gene therapy agents. Now, a variety of drugs for the treatment of AMD-induced GA have entered clinical trials, and this article reviews the progress of clinical trials of complement therapy for GA and its safety and efficacy.