HTRA1 and complement activation in neovascular age-related macular degeneration.

Purpose: To investigate the relationship between high temperature requirement A (HTRA1) and the local complement system, we measured HTRA1 and complement activation products in the aqueous humor of patients with neovascular age-related macular degeneration (nAMD).

Study Design: Surveys (cross-sectional studies).

Methods: One hundred twenty-one eyes of 121 patients with nAMD and 55 control eyes were enrolled. HTRA1, complement activation products (C3a and C4a), and proinflammatory cytokines (vascular endothelial growth factor [VEGF] and monocyte chemoattractant protein-1) were measured. Genotyping of ARMS2 A69S, in linkage disequilibrium with the HTRA1 gene, was performed in all patients and controls.

Results: The respective GG, GT, and TT genotypes for ARMS2 A69S were distributed as follows: 23 (19.0%), 54 (44.6%), and 44 (36.4%) in nAMD patients, and 26 (47.3%), 22 (40.0%), and 7 (12.7%) in controls, (p < 0.001). HTRA1 concentrations in the aqueous humor were higher in nAMD (994 pg/ml; interquartile range, 743-1450) than controls (794 pg/ml; 490-1325). The difference in the HTRA1 concentrations in the aqueous humor between each genotype of ARMS2 A69S was not significant (GG genotype: 857 pg/ml; 508-1115, GT genotype: 957 pg/ml; 758-1474, TT genotype: 1,141 pg/ml; 757-1663, p = 0.1417). VEGF and C3a concentrations in the eyes with the risk allele (T allele) were significantly higher than those with the non-risk allele (p = 0.0400 and p = 0.0197, respectively). HTRA1 concentration was correlated with only the VEGF concentration (ρ = 0.3651, p < 0.0001).

Conclusion: Concentrations of HTRA1 in the aqueous humor were not increased in patients with the ARMS2 risk allele and did not correlate with C3a and C4a concentrations. HTRA1 concentrations in aqueous humor do not reflect local complement activation in nAMD.