August 15, 2022

Mitochondria and retinal degeneration

Vanderbilt researchers have developed a new cellular model for exploring mitochondrial dysfunction in age-related macular degeneration, the leading cause of blindness in people over 65.

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over 65. Dysfunction of energy-producing mitochondria and damage to mitochondrial DNA in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of AMD, but current in vitro models have limitations. 

To better model mitochondrial dysfunction in AMD, Edward Chaum, MD, PhD, and colleagues used pluripotent stem cells from patients with a mitochondrial disorder, which they then differentiated into RPE cells. 

Using their cell model, the researchers demonstrated an improved understanding of mitochondrial bioenergetics and clearance (mitophagy) in RPE degeneration and identified a more physiologically relevant model revealing important signaling mechanisms that impact RPE cell aging. 

The findings, reported in Stem Cell Research & Therapy, show that the model system is a powerful tool for exploring mitochondrial dysfunction in AMD and suggest that therapies aimed at activating RPE mitophagy may be useful for preventing or treating AMD.

Other authors of the study from the Department of Ophthalmology and Visual Sciences at VUMC are Sujoy Bhattacharya, PhD, Jinggang Yin, PhD, and Weihong Huo. 

The research was supported by a Shulsky Foundation research grant, the Potocsnak Family Vision Research Center at the Vanderbilt Eye Institute, the Margy Ann and J. Donald M. Gass Chair endowment, National Institutes of Health (Vanderbilt Vision Research Center Core Grant EY008126), and an unrestricted departmental research grant from Research to Prevent Blindness, Inc.