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

被引：61

作者：

Kim, Benjamin J. ^{[1
]}

Mastellos, Dimitrios C. ^{[2
]}

Li, Yafeng ^{[1
]}

Dunaief, Joshua L. ^{[1
]}

Lambris, John D. ^{[3
]}

机构：

[1] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Natl Ctr Sci Res Demokritos, Athens, Greece

[3] Univ Penn, Dept Lab Med & Pathol, Perelman Sch Med, Philadelphia, PA USA

来源：

PROGRESS IN RETINAL AND EYE RESEARCH | 2021年 / 83卷

基金：

美国国家卫生研究院;

关键词：

Age-related macular degeneration; Geographic atrophy; Complement; C3; C5; Retina; PIGMENT EPITHELIAL-CELLS; MEMBRANE ATTACK COMPLEX; GEOGRAPHIC ATROPHY SECONDARY; FACTOR-H POLYMORPHISM; CHOROIDAL BLOOD-FLOW; MACULAR-DEGENERATION; ALTERNATIVE PATHWAY; NLRP3; INFLAMMASOME; OXIDATIVE STRESS; FACTOR-B;

D O I：

10.1016/j.preteyeres.2020.100936

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

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.

引用

页数：22

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