Transcriptional Regulation of Anti-Oxidant Genes in the RPE

Oxidative stress as a result of declined antioxidant defenses in aged retinal pigmented epithelia (RPE) plays an etiological role, causing or contributing to age-related retinal degeneration (AMD). This research is aimed at revealing a novel coordinator of the antioxidant system in the RPE and indicating its role in human AMD. These studies are expected to provide critical information for developing new therapies that can target multiple antioxidant genes to preserve retinal function and prevent/treat AMD.

Grantee institution at the time of this grant: University of Oklahoma Health Sciences Center

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 the normal functioning of the RPE and the retina. To counteract such oxidative damage, cells are equipped with a potent defense system that consists of multiple antioxidant 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 antioxidant system of the RPE and reveal its role in the development of human AMD. These studies are expected to reveal a new therapeutic target that can enhance multiple antioxidant genes in the RPE and to develop gene therapies to effectively protect cells against oxidative damage and to prevent and treat AMD.