Cellular Self-Eating: An Important Mechanism in Age-Related Macular Degeneration

Nady Golestaneh, PhD
Georgetown University (Washington, DC)
Year Awarded:
2014
Grant Duration:
July 1, 2014 to June 29, 2017
Disease:
Macular Degeneration
Award Amount:
$120,000
Grant Reference ID:
M2014039
Award Type:
Standard
Award Region:
US Northeastern
Nady Golestaneh, PhD

Autophagy, a Critical Pathway in the Pathophysiology of Age-Related Macular Degeneration

Summary

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. More than 11 million Americans are affected by AMD, and there is relatively little in the way of effective treatment until the disease become advanced. Autophagy is a self-eating process in the cells that involves degradation of unwanted cellular components to supply the cell with energy when needed. Failure in autophagy is related to diseases. We propose to study the role of autophagy and its possible dysfunction in AMD.

Details

This research is directed towards investigating the role of autophagy in the pathophysiology of age-related macular degeneration (AMD). Autophagy is a self-degradation process that breaks down cellular components to ensure cell survival during starvation. Autophagy also plays a housekeeping role in clearing damaged organelles, and is implicated in diseases that include cancer and metabolic and neurodegenerative disorders, in addition to normal aging. Dr. Golestaneh and colleagues have generated a physiologically relevant “disease in a dish model” that will allow to directly measure the efficiency of autophagy and its dysfunction in AMD. Determining dysfunction in autophagy and its underlying pathways will lead to better understanding the mechanisms of the disease and may lead to development of new drugs for treatment of AMD.

Details. The goal of this project is to examine the implication of autophagy in the pathophysiology of AMD. To do this, Dr. Golestaneh and colleagues are evaluating the efficiency of autophagy in degrading the proteins, lipids, and organelles, such as mitochondria, in retinal pigment epithelium (RPE) from AMD donors and comparing that with normal RPE. By comparing the efficiency of autophagy in diseased and normal RPE, the team aims to identify specific dysfunctional pathways, culprits in accumulation of waste products, called drusen, the hallmark of dry AMD. Because damage in mitochondria, the cellular energy producers, might also influence the efficiency of autophagy, the scientists are also examining mitochondrial function in AMD and the effect of mitochondrial activators and inhibitors on the efficiency of autophagy in diseased and normal RPE.

To date, little is known about the role of autophagy in the pathophysiology of AMD. This is mainly due to the lack of an adequate human in vitro AMD disease model that recapitulates many aspects of this multifactorial disease. The team has overcome this limitation by developing a physiologically relevant human AMD “disease in a dish” model that is a unique and reliable resource to study the role of autophagy in AMD.

This study supported by BrightFocus Foundation is directly investigating autophagy in a human AMD disease model, and will be able to establish whether the pathophysiological phenotypes identified by the research team in the diseased RPE are due to impaired autophagy. The successful completion of this project may lead to the discovery of new treatment strategies for AMD.

About the Researcher

Nady Golestaneh is an assistant professor and director of research at the Department of Ophthalmology, Georgetown University School of Medicine. She also has secondary appointments at the Departments of Neurology and Biochemistry there. She earned her BS from University of Jussieu Paris VII, and her MS and PhD in biology and pharmacology of aging from University of Paris VI, Pierre et Marie Curie, in Paris France. She performed postdoctoral fellowships at the National Eye Institute (NEI) of the National Institutes of Health’s (NIH), Johns Hopkins University, and Georgetown University. Dr. Golestaneh’s research team is focused on understanding the disease mechanisms of AMD by using human retinal pigment epithelium (RPE) and stem cell technology to delineate specific pathways and signaling that are impaired in RPE during AMD. Dr. Golestaneh’s long-term goal is to develop new drugs for treatment of this devastating neurodegenerative disease. Prior to her BrightFocus Foundation award, Dr. Golestaneh received grants from Prevention of Blindness, and NEI/NIH.
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