Linking the microbiome to the complement system in geographic atrophy

Age-related macular degeneration (AMD) is the leading cause of vision loss in the aged population with the late stage geographic atrophy (GA). Risk factors for AMD include age, genetic variants in the complement system, nutritional factors, and alterations in the gut microbiome (GM). To identify taxonomic and functional differences in the microbiome associated to disease pathophysiology and genetic risk factors, this study investigated the GM and the ocular surface microbiome (OSM) of GA patients compared to healthy controls by whole-metagenome shotgun sequencing. 16 AMD-associated SNPs were genotyped from blood samples using TaqMan assays and Sanger sequencing. While GA patients showed differences in the GM, and altered metabolic pathways including inosine 5'-phosphate degradation, NAD salvage, and ketogenesis, no alterations in the OSM were found. Genetic analysis associated SNP rs1061170 in the complement factor H gene with GA. These findings suggest that microbial alterations may contribute to GA through inflammation and oxidative stress.Registry: ClinicalTrials.gov, NCT02438111, Registration date: 28 April 2015, and NCT04658238, Registration date: 01 December 2020.