Abstract
A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.
Highlights
Age-related macular degeneration is the leading cause of blindness in the industrialized countries [1]
Based on these results we hypothesized that choroidal blood flow (ChBF) regulation is abnormal in young healthy carriers, homozygous for the C risk-allele of rs1061170
The present study indicates significant differences in the regulatory behavior of ChBF during an increase in ocular perfusion pressure (OPP) depending on rs1061170 genotyping
Summary
Age-related macular degeneration is the leading cause of blindness in the industrialized countries [1]. A single nucleotide polymorphism (SNP), rs1061170 ( known as Y402H), located within the chromosome 1q32 region and corresponding to the human complement factor H gene, was found to be associated with AMD This supports the hypothesis that a local inflammatory process is involved in AMD pathogenesis. Alterations in the retinal and choroidal vessels were already visible in 3 month old animals and became more pronounced after 12 months Based on these results we hypothesized that choroidal blood flow (ChBF) regulation is abnormal in young healthy carriers, homozygous for the C risk-allele of rs1061170. This hypothesis was tested by studying the response of ChBF, as measured with laser Doppler flowmetry, during an isometric exercise-induced increase in blood pressure [18,19,20,21]
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