Finally, we found a significantly lower arterial response to flicker stimulation in TT homozygotes for the
ARMS A69S polymorphism and a less prominent venous response to flicker stimulation in patients with TC + CC genotypes in the
CFH Y402H polymorphism. Carriers of at least one high-risk C allele in the Y402H variant are two to three times more likely to develop AMD than homozygous individuals with T alleles,
58 whereas individuals harboring TT alleles in the
ARMS A69S polymorphism have up to a 10-fold increase in the risk of late AMD. Our results suggest that high-risk alleles in these polymorphisms are associated with decreased arterial or venous responses to flicker stimulation, however this does not necessarily mean a causal relationship. In population-based trials, the pathways surrounding venous retinal microcirculation maladaptation have demonstrated strong correlations with indicators of systemic inflammation,
59,60 which corresponds to the function of
CFH and
ARMS2, as
CFH is a crucial regulator of the complement system, whereas
ARMS2 might also play a role in the pro-inflammatory pathway.
61,62 Although there have been several studies conducted in murine models on the role of
CFH in retinal development and function,
63,64 there is less evidence of the influence of
CFH on retinal vessel parameters in humans. Only one study investigated retinal vessel dilation in healthy young carriers of the C risk allele at the Y402H polymorphism and found no abnormal flicker-induced retinal vessel dilation
28; however, the study included only 18 homozygous C carriers. We cannot exclude the possibility that the vascular response could alter over the lifespan of these individuals and be poorer when they develop AMD. To the best of our knowledge, our study provides the first evidence that high-risk alleles in the
CFH Y402H and
ARMS2 A69S polymorphisms are associated with decreased arterial or venous responses to flicker stimulation in a population of patients with AMD.