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Jianhai Du, Whitney Cleghorn, Guy Chan, Jonathan Linton, Martin Sadilek, Viren Govindaraju, James Hurley; Retinal metabolic pathways: a comparative study with cerebellum, hippocampus and olfactory bulb. Invest. Ophthalmol. Vis. Sci. 2013;54(15):691.
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To compare how retinas use different types of fuels for energy metabolism and to compare the fuel preferences of retinas and other types of neurons.
Mouse retina, cerebellum, hippocampus and olfactory bulb were isolated and cultured in Krebs-Ringer bicarbonate (KRB) buffer. The retina and other neurons were incubated with 5 mM of a variety of 13C labeled fuel sources. Rat retinas were isolated and incubated in KRB buffer and sectioned at 50 micron thickness. Metabolites from both the tissue and the medium were extracted and measured by GC-MS. Results were corrected for the natural abundance of isotopes. The overall enrichment and the distribution of labeled carbons in each metabolite were calculated.
Retinas converted glucose to lactate and pyruvate and released them into the medium ~4 times higher than other neurons. Unlike other neurons retinas did not release glutamate. Retina had the highest rate of 13C enrichment of the mitochondrial TCA cycle intermediates from glucose among all the neurons. By incubating retinas and other neurons with the same concentration of 13C glucose, 13C glutamine, 13C pyruvate or 13C lactate for 2 hours, we found the 13C glutamine produced the highest 13C enrichment of succinate, fumarate and malate. In the retina, glutamine robustly competed with glucose for enrichment of all mitochondrial intermediates except citrate. By incubating with 12C glucose together with 13C glutamine, we found that retinas had the highest rate of 13C enrichment in mitochondrial intermediates of all the types of neurons we tested. Furthermore, rat retina sections showed that glutamine labeling was localized primarily in the mitochondrial intermediates in the photoreceptor layer.
The retina has much higher metabolic rate from both glucose and glutamine than other neurons. The retina, particularly the photoreceptor layer, selectively uses glutamine over glucose, pyruvate and lactate to fuel mitochondria.
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