Chronic hypoxia and consequent accumulation of hypoxia inducible factor (HIF)-α (e.g., HIF-1α and HIF-2α) in RPE cells may be central AMD risk factors showing Bruch’s membrane thickening and metabolic changes (i.e., lipid accumulation, VEGF upregulation) in RPE limit glucose delivery to photoreceptors [29]. The gene discussed is VEGFA; the disease is age-related macular degeneration.