RPE cells are highly metabolically active and contain large numbers of mitochondria, which are the primary source of endogenous ROS.37 Our results revealed that AMD cybrids have: (1) elevated levels of mitochondrial superoxides, the predominant ROS found in the mitochondria, and (2) reduced expression of antioxidant genes, PRDX3 and SOD2. Together these data represent an imbalance between mitochondrial ROS production and antioxidant enzyme levels, which would lead to significantly higher oxidative stress within AMD cybrids compared to the controls. Here, SOD2 is linked to age-related macular degeneration.