Energy metabolism is essential for viability and function of retinas. Earlier studies of retinal metabolism revealed a predominance of aerobic glycolysis and higher rates of energy consumption in darkness than in light. New technologies have been developed since those pioneering studies. We're using mass spectrometry and other state-of-the- art techniques to investigate retinal energy metabolism in ways that were not possible in previous studies. Symbiotic metabolic relationships between neurons and glia are important for function and survival of neuronal tissues. In the retina photoreceptors die when Muller cells are ablated and the metabolic state of Muller cells changes when photoreceptors degenerate. One of the important functions of glia is to synthesize glutamine. In brain a metabolic cycle known as the Astrocyte Neuronal Lactate Shuttle explains the metabolic relationship between glia and neurons. However, the unusual morphology and metabolic requirements of the outer retina create unique metabolic requirements for photoreceptors and Muller cells. We have found evidence that aspartate produced by retinal neurons may play an important role in the relationship between neurons and Muller cells in retinas.
Our first aim i s to test the hypothesis that an aspartate/glutamine cycle shuttles carbons between neurons and Muller cells in retina. Metabolic demands of vertebrate retinas are different in darkness and in light. In darkness the demand for ATP is high as photoreceptors use it to fuel active ion pumps. In light, ATP demand is lower, but metabolites must be diverted for production of reducing power to fuel regeneration of rhodopsin and to synthesize phospholipids and other metabolic building blocks. During the previous funding period we made the novel observation that the metabolism of purine nucleotides is strongly influenced by illumination.
Our second aim i s to identify the mechanism by which purine metabolism is regulated by darkness and light. We will identify the mechanism by which darkness and light influence purine metabolism in retinas.
Photoreceptors have unique metabolic requirements that change dramatically in darkness vs. in light. Findings from our studies will expedite the understanding of the underlying causes of retinal disease and provide a framework for understanding what photoreceptors require for viability and function.
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