Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.

Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions.
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针对视网膜的靶向补充组件C3和C5:关键概念和挥之不去的问题。

DOI:
10.1016/j.preteyeres.2020.100936
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发表时间:
2021-07
影响因子:
17.8
通讯作者:
Lambris JD
Lambris JD
中科院分区:
医学1区
文献类型:
--
作者:
Kim BJ;Mastellos DC;Li Y;Dunaief JL;Lambris JD

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视网膜相关性黄斑变性(AMD)仍然是法律的失明的主要原因,并且对AMD的地图状萎缩形式的治疗是显著未满足的需求。补体级联的失调被认为是AMD病理生理学的工具。特别地,C3和C5是补体级联的关键组分,并且已经成为AMD的主要治疗靶标。在这篇文章中,我们详细讨论了C3和C5,包括它们在AMD中的作用,生化和结构方面,表达的位置,以及C3和C5片段的功能。此外,文章批判性地回顾了开发针对C3和C5的治疗方法,强调了在C3水平广泛抑制补体与在C5更特异性抑制补体的潜在影响。补体生物学与炎性小体和小胶质细胞/巨噬细胞活性的关系突出显示。重点介绍了C3和C5生物学的概念,并指出了需要解决的问题和今后研究的方向。
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.
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