Models of Energy Metabolism in Retina

Abstract

Abstract: : Purpose: Lactate, not CO₂, is quantitatively the major product of the in vitro aerobic metabolism of glucose in vertebrate retinas, in photoreceptorless (RCS) rat retinas, and in monolayer cultures of Müller and RPE cells. From these studies, we and others have concluded that there is a net production of lactate from retinal neurons and glia. A different view (termed metabolic coupling) is that Müller cells are the exclusive producers of lactate, which then serves as the substrate (net utilization) for CO₂ production in the mitochondria in the inner segments of photoreceptors and other retinal neurons. A corollary of the metabolic coupling hypothesis is that rods do not take up glucose. Our purpose therefore was to test further these very disparate views of the metabolism of glucose and lactate. Methods: Rat eyecups (retina/choroid/sclera) were incubated in bicarbonate-buffered, oxygenated media of normal ionic composition in the presence of ₁₄C-glucose (10 mM) or ₁₄C- lactate (10 mM) and the production of ₁₄CO₂ was measured using different combinations of labeled and unlabeled substrates. Measurements were also made of lactic acid production and retinal ATP content under the different substrate conditions. ₃H-2-deoxyglucose autoradiography was carried out using rat and guinea pig eyecups. Results: Incubation of these eyecups with ₃H-2-deoxyglucose revealed autoradiographic grains over all cell types and plexiform layers, including the RPE and inner and outer segments; there were no obvious differences in the distribution of grains between dark- and light-adapted retinas. Rat eyecups produced lactate at an averaged rate of 1.8 µmoles lactate/hr/eyecup, whether the starting ambient concentration of lactate was 0 or 10 mM. The averaged rates of ₁₄CO₂ formation (expressed as µmoles ₁₄C-substrate oxidized/hr/eyecup) were as follows: 1) with ₁₄C-glucose, 0.052; 2) with ₁₄C-glucose and lactate (unlabeled), 0.031; 3) with glucose (unlabeled) and ₁₄C-lactate, 0.028. Retinal ATP content was similar in retinas incubated with either glucose alone or with glucose and lactate. Conclusion: All retinal cell types appear to take up and phosphorylate glucose. There is production of lactate from glucose, and formation of CO₂ from glucose or lactate by mitochondria in rat eyecups, results consistent with the metabolic coupling hypothesis. Nevertheless, we suggest that the production of ₁₄CO₂ from ₁₄C-lactate in this tissue under the normal condition of glucose availability results from equilibration of lactate with carbon metabolism via pyruvate pools rather than from net utilization.

Keywords: 554 retina • 467 metabolism