Age-related macular degeneration (AMD) remains a major cause of legal blindness, and treatment for the geographic atrophy form of AMD is a significant unmet need. Dysregulation of the complement cascade is thought to be instrumental for AMD pathophysiology. In particular, C3 and C5 are pivotal components of the complement cascade and have become leading therapeutic targets for AMD. In this article, we discuss C3 and C5 in detail, including their roles in AMD, biochemical and structural aspects, locations of expression, and the functions of C3 and C5 fragments. Further, the article critically reviews developing therapeutics aimed at C3 and C5, underscoring the potential effects of broad inhibition of complement at the level of C3 versus more specific inhibition at C5. The relationships of complement biology to the inflammasome and microglia/macrophage activity are highlighted. Concepts of C3 and C5 biology will be emphasized, while we point out questions that need to be settled and directions for future investigations.

年龄相关性黄斑变性 (AMD) 仍然是导致法定失明的主要原因，而地理萎缩型 AMD 的治疗是一个未得到满足的重大需求。补体级联失调被认为有助于 AMD 病理生理学。特别是，C3 和 C5 是补体级联的关键组成部分，已成为 AMD 的主要治疗靶点。在本文中，我们详细讨论 C3 和 C5，包括它们在 AMD 中的作用、生化和结构方面、表达位置以及 C3 和 C5 片段的功能。此外，该文章批判性地回顾了针对 C3 和 C5 的开发疗法，强调了在 C3 水平广泛抑制补体与在 C5 水平更特异性抑制相比的潜在影响。强调了补体生物学与炎症小体和小胶质细胞/巨噬细胞活性的关系。将强调 C3 和 C5 生物学的概念，同时指出需要解决的问题和未来研究的方向。