Estimation of systemic complement C3 activity in age-related macular degeneration

Objectives: To determine the role of systemic complement activation in the pathogenesis of age-related macular degeneration and to examine whether serum C3a des Arg reflects systemic complement activation, independent of individual complement component levels. Methods: Plasma complement C3a des Arg levels and a single nucleotide polymorphism at position 402 of the complement factor H gene (CFH) were determined in 3 groups of subjects: 42 subjects with early age-related maculopathy, 42 subjects with neovascular (wet) agerelated macular degeneration, and a control group of 38 subjects with no clinical evidence of age-related changes at the macula. Results: The median (range) of plasma complement C3a des Arg levels in the age-related maculopathy and neovascular age-related macular degeneration groups were 52.6 (2.8-198.1) ng/mL and 60.9 (3.1-173.1) ng/mL, respectively. The levels were significantly raised compared with the control group (n = 38), which had a median (range) plasma complement C3a des Arg level of 40.3 (6.1-81.7) ng/mL (analysis of variance, P = .02). The concentration of plasma C3a des Arg did not differ significantly between those with different CFH genotypes (P =.07). Conclusion: Systemic activation of the complement system may contribute to the pathogenesis of age-related macular degeneration independent of CFH polymorphism. Clinical Relevance: The results of this study may be relevant to aiming new treatment strategies toward reducing systemic low-grade inflammation.