Complement regulatory proteins are associated with progression rate of geographic atrophy secondary to age-related macular degeneration

Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive degenerative disease leading to irreversible vision loss in elderly individuals. The complement system, including the alternative pathway (AP) forms an essential part of the innate immune system. Since dysregulation of the complement system has been strongly associated with the development and progression of GA, we sought to investigate the expression of specific regulators of the complement system, known as complement regulatory proteins (Cregs), in relation to progression rate (PR) of disease in patients with GA. Using flow cytometry, we determined the proportion of Cregs on peripheral blood leukocytes drawn from patients with GA. Patients were genotyped for risk-associated SNP (CFH rs1061170, ARMS2 rs10490924) and serial fundus autofluorescence images were used to determine the PR of atrophic lesions. Patients with fast GA progression had a lower proportion of CD59 on CD8 + T cells compared to patients with slow progression of disease (p = 0.025), suggesting that dysregulated CD59 could be involved in progression of GA. Patients with high-risk CFH genotypes had a higher proportion of CD59 on classical monocytes compared to patients carrying the low-risk genotype (p = 0.044). Our findings indicate that GA progression is associated with dysregulation of complement regulators, and Cregs could serve as a novel target for treatment of GA. However, further studies are needed to elucidate their role in GA pathogenesis and to evaluate their potential as future complement-targeting drugs.