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Robert James Casson, Glyn Chidlow, Guoge Han, Thaksaon Kittipassorn, Dan Peet, John Peter Wood; Pyruvate Kinase and Lactate Dehydrogenase Isoenzymes in Mammalian Retina: Novel Metabolic Implications. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5430.
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© ARVO (1962-2015); The Authors (2016-present)
Like cancer cells, photoreceptors display a high glycolytic flux and produce lactate despite the presence of oxygen (the Warburg effect). This phenomenon is dependent on lactate dehydrogenase (LDH), which comprises subunits LDHA and LDHB; LDHA predominates in glycolytically active cells. To our knowledge, cell-specific localization of LDHA and LDHB in the mammalian retina has not been reported. A related phenomenon in cancer cells is the ability to utilize glycolytic intermediates for biomass production rather than energy production, a property known as the "metabolic budget system". The molecular switch serving this function is an isoenzyme of pyruvate kinase (PK), known as PKM2. In this study we determine the expression and localization of PK and LDH isoenzymes in mammalian retina and make comparisons with the brain.
Single- and double-labeling immunohistochemistry and Western blotting for PKM2, pyruvate kinase M1 (PKM1), LDHA, and lactate dehydrogenase B (LDHB) were performed on retinal and brain sections from C57BL/6 mice, Sprague-Dawley rats and marmosets. Several commercially available antibodies were studied and optimized. PKM2 mRNA was quantified in rodent retina and brain using qPCR.
PKM2 was localized to glial cells and photoreceptors in the retina of all 3 species, whereas it was exclusively glial in the brain. PKM1 was confined to neurons in the retina and brain. LDHA was principally found in photoreceptors, whereas LDHB was principally in the inner retina. The presence of high levels of PKM2 and LDHA in the retina was confirmed on Western blotting. There was a 6 to 9-fold greater expression of PKM2 mRNA in the rodent retina compared to brain.
The mammalian photoreceptors contain PKM2 and LDHA. This is consistent with their known high glycolytic rate and provides circumstantial evidence for the presence of a metabolic budget system involving glycolytic intermediates in opsin synthesis.
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