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. 2011 Oct;93(4):565-7.
doi: 10.1016/j.exer.2011.06.015. Epub 2011 Jun 26.

Elevated membrane attack complex in human choroid with high risk complement factor H genotypes

Robert F Mullins  1 , Aaron D Dewald, Luan M Streb, Kai Wang, Markus H Kuehn, Edwin M Stone
Affiliations

Elevated membrane attack complex in human choroid with high risk complement factor H genotypes

Robert F Mullins et al. Exp Eye Res. 2011 Oct.

Abstract

Data from human genetics, histopathology, and animal models reveal a major role for the complement system in the development of age-related macular degeneration (AMD). Genetic variations in the complement factor H (CFH) gene are associated with an elevated risk of AMD. In this study we sought to determine whether eyes from donors with a high-risk genotype (homozygosity for the histidine allele at codon 402) exhibit altered levels of membrane attack complex (MAC) in the choroid, compared to eyes with a low risk genotype (homozygosity for tyrosine). Proteins were extracted from the RPE/choroid of 18 donors (10 low risk and 8 high risk) and levels of MAC were assessed using an ELISA assay. Eyes from donors homozygous for the histidine allele showed 69% higher levels of MAC than those homozygous for the tyrosine allele (p < 0.05), independent of whether the eyes showed signs of early AMD. Our results provide evidence that high-risk CFH genotypes may affect AMD risk by increased deposition of MAC around the aging choriocapillaris.

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Figures

Figure 1
Figure 1. MAC associated with CFH genotype in the human RPE-choroid
A, B Graphs showing normalized levels of MAC in human RPE-choroid. Levels of MAC were significantly elevated in donor eyes homozygous for the high risk (HH) allele compared to the low risk (YY) allele (A). The presence of early AMD was associated with a trend toward increased levels of MAC but this did not reach statistical significance. Asterisks indicate mean value. C–F, Distribution of the membrane attack complex (green fluorescence) in donor maculae. In most cases, MAC is localized to domains surrounding the choriocapillaris in both HH (C, D) and YY (E, F) homozygotes. Drusen (arrows) are often immunoreactive. Yellow-orange fluorescence indicates RPE lipofuscin and blue fluorescence is due to the nuclear counterstain diamidino-phenol-indole. CC, choriocapillaris. Scale bar = 50μm.
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