Skeie Jessica M, Fingert John H, Russell Stephen R, Stone Edwin M, Mullins Robert F
Department of Biomedical Engineering, University of Iowa College of Engineering, Iowa City, Iowa, USA.
Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5336-42. doi: 10.1167/iovs.10-5322. Epub 2010 May 19.
The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). In this study, the authors sought to evaluate the pathophysiologic roles of complement components C3a and C5a in the human choroid in AMD.
Human RPE/choroid was assayed for the presence of C3a and C5a receptors (C3aR and C5aR) using RT-PCR and immunohistochemistry. Choroidal endothelial cell migration and proliferation were evaluated in the presence of C5a. Organ cultures of human choroid were incubated in C5a or bovine serum albumin (BSA) followed by quantitative immunohistochemistry and quantitative PCR for ICAM-1. AMD patients and controls were genotyped at SNPs in the C5R1 and C3AR1 genes.
C5aR, but not C3aR, was detected in human choroid. C5a did not promote endothelial cell migration or proliferation. However, choriocapillaris endothelial cells in organ culture responded to C5a by increasing ICAM-1 mRNA and protein. No significant association of SNP genotypes was detected in AMD patients at the C3AR1 and C5R1 genes.
The generation of C5a peptides may lead to activation of choriocapillaris endothelial cells in AMD. Activation of the choroidal endothelium may affect the progression of AMD by recruitment of monocytes, leading to additional sequelae of AMD pathogenesis.
补体系统在年龄相关性黄斑变性（AMD）的进展中起关键作用。在本研究中，作者试图评估补体成分C3a和C5a在AMD患者脉络膜中的病理生理作用。
采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法检测人视网膜色素上皮细胞/脉络膜中C3a和C5a受体（C3aR和C5aR）的存在情况。在C5a存在的情况下评估脉络膜内皮细胞的迁移和增殖。将人脉络膜器官培养物在C5a或牛血清白蛋白（BSA）中孵育，随后进行ICAM-1的定量免疫组织化学和定量聚合酶链反应（PCR）。对AMD患者和对照组进行C5R1和C3AR1基因单核苷酸多态性（SNP）基因分型。
在人脉络膜中检测到C5aR，但未检测到C3aR。C5a未促进内皮细胞迁移或增殖。然而，器官培养中的脉络膜毛细血管内皮细胞对C5a有反应，ICAM-1 mRNA和蛋白增加。在AMD患者中，未检测到C3AR1和C5R1基因的SNP基因型有显著关联。
C5a肽的产生可能导致AMD患者脉络膜毛细血管内皮细胞活化。脉络膜内皮细胞的活化可能通过募集单核细胞影响AMD的进展，导致AMD发病机制的其他后遗症。
