Identifying Cell-protective Compounds for the Treatment of AMD

Donald Zack, MD, PhD
Wilmer Eye Institute (Baltimore, MD)
Year Awarded:
2011
Grant Duration:
July 1, 2011 to June 30, 2013
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2011077
Award Type:
Standard
Award Region:
US Northeastern

Co-principal Investigators

Cindy J Berlinicke, PhD
Johns Hopkins University

High Content Screen for RPE Cell Protective Compounds

Summary

One of the early changes associated with dry AMD is alteration and damage of the retinal pigmented epithelial (RPE) cells, the cells responsible for maintaining the delicate environment necessary to sustain the health and function of photoreceptors. Treatment strategies that promote RPE integrity and function offer great promise, but no such treatments have yet been shown to be effective. As a first step towards developing such a strategy, we propose to develop and perform experiments that will allow us to identify factors that can protect RPE cells from AMD-associated stress.

Details

Retinal pigment epithelial (RPE) cells are essential for normal retinal function, being responsible for maintaining the delicate balance between waste removal and nutrient delivery that is necessary to sustain the health and function of photoreceptors. Dysfunction and death of RPE cells plays an important role in the etiology of age‐related macular degeneration (AMD). There are no known drugs that effectively prevent this AMD‐associated RPE dysfunction and cell death. Drs. Donald Zack, Cindy Berlinicke, and colleagues propose to identify small molecules, potential drugs that can promote the health and survival of RPE cells. These researchers will look for these protective small molecule drugs by screening thousands of candidates with an automated, robotic microscope system. The identity of effective candidates could give clues to understanding what causes AMD and also could provide candidate molecules that could be developed into novel drug treatments for AMD.

Research Updates

In the first step towards a dry AMD treatment strategy to promote RPE integrity and function, Dr. Zack’s and Dr. Berlinkicke’s team has developed an assay in which cultured RPE cells are injured by oxidative stress. They began testing collections of small molecules to identify compounds that can promote the survival and function of the stressed RPE cells. Using this assay, the team has had some preliminary success in identifying molecules that promote RPE survival. They are now actively continuing this work, characterizing the already identified molecules, and screening for additional, hopefully more potent, protective molecules. Drs. Zack and Berlinkicke hope that molecules identified through this screen will be lead candidate compounds for the development of new strategies for the treatment of dry AMD.