Macular Degeneration Research
Sarah Zhang, M.D.
University of Oklahoma Health Sciences Center
Oklahoma City, OK
Title: Transcriptional regulation of anti-oxidant genes in the RPE
Non-Technical Title: A novel strategy to protect the RPE in AMD
Duration: April 1, 2010 - June 15, 2012
Award Type: Standard
Award Amount: $100,000
Oxidative stress as a result of declined anti-oxidant 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 anti-oxidant 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 to prevent/treat AMD.
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.
Zhong, Y., Wang, J.J., Li, J., Chen, C., Mandal, M.N., Le, Y., Anderson, R.E., and Zhang, S.X. (2012) Deficiency of X-box binding protein 1 induces oxidative damage of the RPE: implications in age-related retinal degeneration. PlosOne, 7(6): e38616. doi:10.1371/journal.pone.0038616.
Jing G, Wang JJ and Zhang SX. Endoplasmic reticulum (ER) stress and retinal cell apoptosis. Exp. Diabetes Res., (Invited review), 2012;2012:589589. Epub 2011 Dec 14.
Zhong Y, Wang JJ, Li J, Chen C, Ratan R and Zhang SX. Activation of Endoplasmic Reticulum Stress by Hyperglycemia is Essential for Inflammatory Cytokine Production in Müller cells in Diabetes. Diabetes, 2012; 61(2):492-504. 2012 Jan 6.
Chen YM, Wang JJ, Li J, Ratan R, Townes T and Zhang SX. Activating transcription factor 4 is a novel regulator of inflammatory genes in diabetic retinopathy. Diabetologia, 2012;55(9):2533-45. Epub 2012 Jun 4.