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Andrei O. Chertov, Lars C. Holzhausen, Ian R. Sweet, Ed Parker, Martin Sadilek, James B. Hurley; What Keeps A Photoreceptor Alive? I. Requirements For Mitochondrial Activity And Anabolic Substrates. Invest. Ophthalmol. Vis. Sci. 2011;52(14):526.
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To understand the metabolic requirements for photoreceptor viability. Photoreceptors do not survive without glucose. We investigated the basis for this by evaluating how photoreceptor viability is influenced by:a. Inadequate concentrations of intracellular ATP.b. Damage to mitochondria or inadequate mitochondrial activity.c. Inadequate concentrations of building blocks for anabolic metabolism.In this study we focused on the importance of mitochondria function and building blocks for anabolic metabolism.
Intact mouse retinas were isolated and incubated in bicarbonate buffered physiological solutions with or without glucose, pyruvate, glutamine, leucine or malate. O2 consumption was measured using a perfusion apparatus. Citric acid cycle intermediates and other metabolites were measured by GC-MS. Cell viability was analyzed using confocal microscopy to quantify propidium iodide uptake in the photoreceptor layer.
Isolated mouse retinas remain viable for more than 8 hours when supplied with glucose. When they are deprived of glucose they gradually stop consuming oxygen, their mitochondria depolarize and they become competent to sequester propidium iodide. During glucose deprivation citric acid cycle intermediates become depleted and aspartic acid accumulates. Fuels that support mitochondrial activities, but not glycolysis or anabolism, restore oxygen consumption, maintain mitochondrial polarization and prevent propidium iodide uptake for 90 minutes. However, mitochondrial fuels cannot maintain photoreceptor viability for 4 hours or more. Electron microscopy analysis and evaluation of the role of autophagy during glucose deprivation indicate that loss of viability during long term glucose deprivation is caused by depletion of building blocks needed for anabolic metabolism .
Mitochondria activity alone is sufficient for short-term photoreceptor viability. Longer term viability has an additional requirement, building blocks for anabolic purposes.
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