The Circulation of Metabolites in the Outer Retina

Abstract

AbstractThe posterior eye contains two metabolic microenvironments, each occupied by a distinct tissue type. Retinal pigment epithelium (RPE)-choroid tissue is connected to the circulatory system and receives plentiful O2and nutrients. Tight junctions formed by the RPE regulate the diffusion of nutrients to the neural retina. Retina tissue consequently exists in an environment with low O2levels and a lower variety of fuels that can support its metabolic needs. Retina explants release lactate and succinate, presumably as an adaptation to a low O2environment where they cannot be fully oxidized. The RPE-choroid is thought to aid retina metabolism by oxidizing these ‘waste’ products. We tested these ideasin vivoby infusing13C-labeled fuels through jugular vein catheters into circulation. By probing the patterns of13C labeling in glycolysis and the TCA cycle from different fuels and genetic models, we found that the retina and RPE do form a cooperative metabolic relationship, where the RPE-choroid oxidizes retina derived succinate but not lactate. Rather than consuming lactate, mouse RPE-choroid may act as a conduit for retina-derived lactate to re-enter circulation and feed more distant tissues.