Regulators of retinal metabolism in healthy and degenerating retinas

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Abstract: 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. AMPK (AMP- activated protein kinase) is a key regulator of metabolism in highly metabolic tissues and is a candidate to regulate metabolism in photoreceptors, and its role in retinal metabolism will be rigorously studied in this proposed project using both gain-of-function and loss-of-function approaches. Peroxisome proliferator-activated receptor gamma coactivator-alpha (PGC-1α) and beta (PGC-1β) are key regulators of mitochondrial biogenesis. Adenosine monophosphate dependent kinase (AMPK) is an important regulator of PGC-1 activity. Our goal in this study is to determine the roles of AMPK and PGC-1 activity in retinal photoreceptors.