Song Delu, Sulewski Michael E, Wang Chenguang, Song Jiantao, Bhuyan Rupak, Sterling Jacob, Clark Esther, Song Wen-Chao, Dunaief Joshua L
The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, PA.
Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
Mol Vis. 2017 Apr 10;23:210-218. eCollection 2017.
The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment.
We assessed the effect of anaphylatoxin C3a receptor (C3aR) and C5a receptor (C5aR) knockout (KO) on light damage-induced migration of microglia/macrophages into the mouse outer retina via immunofluorescence and real-time quantitative PCR.
We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and Cfd, were all upregulated after light exposure. Retinal Iba1-positive microglia/macrophages express receptors for C3a and C5a. Light damage increased the number of retinal Iba1-positive cells and the mRNA levels of Iba1. Compared with the wild-type (WT) mice, these increases were attenuated in the C5aR KO mice but not in the C3aR KO mice.
C5aR but not C3aR promoted the recruitment of microglia/macrophages. These divergent properties of complement anaphylatoxins in the light damage model provide a rationale for testing the differential effects of these receptors in additional retinal and neurodegeneration models.
补体系统参与年龄相关性黄斑变性（AMD）的发病机制。由于活化的小胶质细胞也与AMD相关，我们研究了补体过敏毒素受体与小胶质细胞募集之间的关系。
我们通过免疫荧光和实时定量PCR评估过敏毒素C3a受体（C3aR）和C5a受体（C5aR）基因敲除（KO）对光损伤诱导的小胶质细胞/巨噬细胞向小鼠外视网膜迁移的影响。
我们发现光照后C3、C5、C3aR、C5aR以及补体替代途径的两种激活剂Cfb和Cfd的mRNA水平均上调。视网膜Iba1阳性小胶质细胞/巨噬细胞表达C3a和C5a的受体。光损伤增加了视网膜Iba1阳性细胞的数量以及Iba1的mRNA水平。与野生型（WT）小鼠相比，这些增加在C5aR基因敲除小鼠中减弱，但在C3aR基因敲除小鼠中未减弱。
C5aR而非C3aR促进小胶质细胞/巨噬细胞的募集。补体过敏毒素在光损伤模型中的这些不同特性为在其他视网膜和神经退行性疾病模型中测试这些受体的不同作用提供了理论依据。
