John Ash, PhD
Francis M. Bullard Eminent Scholar Chair in Ophthalmic Sciences & Associate Professor of Ophthalmology
Department of Ophthalmology, University of Florida
Monday, February 3, 2020
11:10 am - 12:30 pm
489 Minor Hall
Metabolic dysfunction in retinal degeneration
The retina has high metabolic activity, and retinal degenerations have been associated with mitochondrial dysfunction, dysregulation of metabolism, and toxic oxidative damage. However, little is known about how metabolism is maintained under normal conditions or is dysregulated in degenerating retinas. Our data show that AMPK is dysregulated in retinal photoreceptors before degeneration. AMPK (AMP-activated protein kinase) is a crucial regulator of metabolism in highly metabolic tissues and is a candidate to regulate metabolism in photoreceptors we have used both gain-of-function and loss-of-function approaches to study this pathway in the retina. We show that activation of AMPK increases glycolysis, induces mitochondrial biogenesis, and promotes photoreceptor protection from inherited retinal degeneration. Peroxisome proliferator-activated-receptor-gamma-coactivator-alpha (PGC-1α) and -beta (PGC-1β) are key regulators of mitochondrial biogenesis and are regulated by AMPK activity. Our studies show that loss of AMPK or PGC-1 disrupts retinal metabolism and results in a slow age-dependent retinal degeneration. Our study provides a mechanistic link between metabolic dysregulation with sensitivity to neural degeneration.