Age-related macular degeneration (AMD) is the main cause of vision loss among the elderly in the Western world. While AMD is a multifactorial disease, the complement system was identified as one of the main pathways contributing to disease risk. The strong link between the complement system and AMD was demonstrated by genetic associations, and by elevated complement activation in local eye tissue and in the systemic circulation of AMD patients. Several complement inhibitors have been and are being explored in clinical trials, but thus far with limited success, leaving the majority of AMD patients without treatment options to date. This indicates that there is still a gap of knowledge regarding the functional implications of the complement system in AMD pathogenesis and how to bring these towards clinical translation. Many different experimental set-ups and disease models have been used to study complement activation in vivo and in vitro, and recently emerging patient-derived induced pluripotent stem cells and genome-editing techniques open new opportunities to study AMD disease mechanisms and test new therapeutic strategies in the future. In this review we provide an extensive overview of methods employed to understand the molecular processes of complement activation in AMD pathogenesis. We discuss the findings, advantages and challenges of each approach and conclude with an outlook on how recent, exciting developments can fill in current knowledge gaps and can aid in the development of effective complement-targeting therapeutic strategies in AMD.

年龄相关性黄斑变性 (AMD) 是西方世界老年人视力丧失的主要原因。虽然 AMD 是一种多因素疾病，但补体系统被确定为导致疾病风险的主要途径之一。遗传关联以及 AMD 患者局部眼组织和体循环中补体激活升高证明了补体系统和 AMD 之间的密切联系。几种补体抑制剂已经并正在临床试验中进行探索，但迄今为止取得的成功有限，使大多数 AMD 患者迄今为止没有治疗选择。这表明关于补体系统在 AMD 发病机制中的功能影响以及如何将其用于临床转化方面仍存在知识空白。体内和体外以及最近出现的源自患者的诱导多能干细胞和基因组编辑技术为研究 AMD 疾病机制和测试未来新的治疗策略开辟了新的机会。在这篇综述中，我们广泛概述了用于了解 AMD 发病机制中补体激活的分子过程的方法。我们讨论了每种方法的发现、优势和挑战，最后展望了最近令人兴奋的发展如何填补当前的知识空白，并有助于制定有效的补体靶向治疗 AMD 策略。