We performed a proteomic analysis of a retinal pigment epithelium cell line (ARPE-19) exposed to long-term sublethal levels of H2O2 to mimic low-level pro-oxidative insult in age-related macular degeneration (AMD). using a wide range of biochemical analyses and cell culture techniques, we highlighted changes in energy metabolism, extracellular matrix organization and inflammation-related processes, which may help in understanding the molecular pathogenesis of AMD.