Friday, May 9, 2025
5/9/2025
Control of Photoreceptor Metabolism - Project Summary/Abstract Photoreceptors consume glucose rapidly because they derive about half of their metabolic energy from the inefficient process of aerobic glycolysis. The retinal pigment epithelium (RPE) is the blood barrier for the outer retina, so glucose from the circulation must pass through it to reach the retina. The ability of the RPE to transport and recycle fuel is essential for homeostasis of the outer retina. Deficiencies in its functions caused either by genetics, by environment factors or by aging cause vision loss. Whereas photoreceptors extract energy from glucose by aerobic glycolysis, the metabolic features of the RPE are complementary. The RPE uses its mitochondria to minimize its own consumption of glucose, presumably so that more glucose can pass through it to reach the retina. Research on retina and RPE metabolism has focused mostly on the immediate use of fuels. However, cells also store metabolic energy, either as glycogen or as fat. RPE cells have both, but we do not know yet how depots of glycogen and fat contribute to normal retina and RPE metabolism and homeostasis. The metabolic relationships between the retina and RPE vary throughout day. We will use both ex vivo and in vivo strategies to quantify diurnal changes in metabolic flux and energy storage in RPE/choroid tissue. In the first aim we will identify diurnal influences on glycogen metabolism. In the second aim we will identify diurnal influences on fatty acid metabolism and in the third aim we will evaluate effects on stored fuels of mutations that cause photoreceptor degeneration and that disrupt RPE phagocytosis. Understanding how the metabolic state and the source of energy, either from blood or from fuels stored in the RPE, may vary with a diurnal or circadian cycle may in future studies be used to develop metabolism-based strategies that make photoreceptors more resilient to stress.
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