Here, we designed to investigate the potential mechanism of SIRT1 in CNV-induced AMD, and our final results demonstrated that SIRT1 elevated LCN2 through SOX9 deacetylation, thereby enhancing cell apoptosis, migration, and angiogenesis of hypoxic cells in vitro and inducing CNV formation in vivo. This evidence concerns the gene LCN2 and age-related macular degeneration.