| First Author | Nishiguchi KM | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 1 | Pages | 508-12 |
| PubMed ID | 22190594 | Mgi Jnum | J:191511 |
| Mgi Id | MGI:5461992 | Doi | 10.1167/iovs.11-8425 |
| Citation | Nishiguchi KM, et al. (2012) C9-R95X polymorphism in patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 53(1):508-12 |
| abstractText | PURPOSE: A non-sense mutation at codon 95 in the gene encoding complement factor C9 (C9-R95X) is found most frequently among Japanese. The authors investigated the association between C9-R95X and Japanese patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: The presence of the C9-R95X polymorphism was assessed by direct sequencing in Japanese patients with either PCV (n = 105) or neovascular AMD (n = 198) and 396 control subjects. Multivariate regression analyses were conducted. Photocoagulation was applied in the eyes of mice with a heterozygous defect in the C3 gene and control wild-type mice. Photocoagulation was also applied to wild-type mice before either anti-C9 antibody or isotype IgG was injected into the eyes. The eyes were collected later for measurement of vascular endothelial growth factor (VEGF) and histological evaluation of choroidal neovascularization (CNV). RESULTS: The frequency of those with one or two C9-R95X variants was lower in neovascular AMD (2.02%) than in PCV (5.71%) and controls (6.05%). The presence of C9-R95X conferred a 4.7-fold reduction (95% confidence interval, 1.2-18.1; P = 0.021) in the risk for neovascular AMD after adjusting for the major AMD risk factors. A heterozygous defect in the C3 gene was associated with the reduced growth of laser-induced CNV, as was intraocular injection of anti-C9 antibody. This reduced CNV growth was accompanied by a decreased level of secreted VEGF in the intraocular fluid. CONCLUSIONS: These findings support the notion that the haploinsufficiency of C9, a terminal complement complex component, engenders reduced intraocular secretion of VEGF and decreased risk for CNV development. |
