Nuclear magnetic resonance and biochemical measurements of glucose utilization in the cone-dominant ground squirrel retina

PURPOSE. To provide quantitative information on glucose utilization in cone-dominant ground squirrel retinas. METHODS. Ground squirrel eyecups were incubated in medium containing C-14-glucose, and the production of (CO2)-C-14 was measured. Measurements were also made of lactic acid production (glycolysis). Nuclear magnetic resonance (NMR) was used to track metabolites generated from C-13-1 glucose. RESULTS. Ground squirrel eyecups produced lactate at a high rate and exhibited normal histology. Light-adaptation reduced glycolysis by 20%. Ouabain decreased glycolysis by 25% and decreased (CO2)-C-14 production by 60%. Blockade of glutamate receptors had little effect on the glycolysis and (CO2)-C-14 produced. When metabolic responses were restricted to photoreceptors, light caused a 33% decrease in (CO2)-C-14 production. The rate of (CO2)-C-14 production was less than 10% of lactate production. Lactate was the major product formed from C-13-glucose. Other C-13-labeled compounds included glutamate, aspartate, glutamine, alanine, taurine, and GABA. Lactate was the only product detected in the medium bathing the ground squirrel retinas. The rod-dominant rat retina exhibited a similar pattern of metabolites formed from glucose. CONCLUSIONS. Lactate, not CO2, is the major product of glucose metabolism in both ground squirrel and rat retinas. Active Na+ transport, however, depends more on ATP produced by mitochondria than by glycolysis. A relatively high fraction of ATP production from glycolysis and glucose oxidation continues in the absence of active Na+ pumping and glutamatergic transmission. Major neurotransmitters are synthesized from the aerobic metabolism of glucose; anoxia-induced impairment in retinal synaptic transmission may be due to depletion of neurotransmitters.