Age-related macular degeneration (AMD) is the leading cause of visual impairment and loss in the elderly. One major risk factor for this sight-threatening disease is increased oxidative stress (accumulation of harmful materials such as reactive oxygen species) in the RPE and the retina. These molecules can damage proteins, lipids and DNA in cells and disturb normal function of the RPE and the retina. To counteract such oxidative damage, cells are equipped with a potent defense system that consists of multiple anti-oxidant genes. However, the function of this defense system declines with age. The aim of this research is to identify a central regulator that coordinates this defense system. Using a combination of tissue culture system and conditional knockout approaches, the studies will delineate if and how a novel “transcription factor” controls the anti-oxidant system of the RPE and to reveal its role in the development of human AMD. These studies are expected to reveal a new therapeutic target that can enhance multiple anti-oxidant genes in the RPE, and to develop gene therapies to effectively protect cells against oxidative damage and to prevent and treat AMD.