PURPOSE: To test the hypothesis that diabetes alters retinal NAD+-to-NADH ratios early in the course of the disease (e.g., the hyperglycemic pseudohypoxia hypothesis). METHODS: In freshly excised age-matched control and diabetic rat retinas, measurements were made of the NAD+ and NADH content as well as a surrogate marker of NAD+-to-NADH ratios obtained from lactate and pyruvate levels. In addition, the effect of various hyperglycemic levels was assessed from measurements of retinal lactate and pyruvate concentrations and the rate of lactic acid production in vitro (isolated rat retinas, monolayer cultures of human retinal pigment epithelial cells, and rabbit lens epithelial cells). RESULTS: No significant differences (P>0.05) were found between control and diabetic tissues in their amount of total NAD+ and NADH/retina, and the ratio of NAD+ to NADH, or in their content of lactate, pyruvate, and adenosine triphosphate (ATP) or in the ratio of lactate to pyruvate. The content of lactate and pyruvate in retinas incubated for 2 hours in media containing 10 or 30 mM glucose was the same as found in fresh tissues, but the levels of these metabolites in retinas incubated in media containing 5 mM glucose declined in comparison to the fresh values. There were no significant differences in lactate content in cultured retinal and lens cells that were exposed to 5 or 30 mM glucose-containing media. DISCUSSION: The present results do not support the hyperglycemic pseudohypoxia hypothesis of diabetic retinopathy.
PURPOSE: To test the hypothesis that diabetes alters retinal NAD+-to-NADH ratios early in the course of the disease (e.g., the hyperglycemic pseudohypoxia hypothesis). METHODS: In freshly excised age-matched control and diabeticrat retinas, measurements were made of the NAD+ and NADH content as well as a surrogate marker of NAD+-to-NADH ratios obtained from lactate and pyruvate levels. In addition, the effect of various hyperglycemic levels was assessed from measurements of retinal lactate and pyruvate concentrations and the rate of lactic acid production in vitro (isolated rat retinas, monolayer cultures of human retinal pigment epithelial cells, and rabbit lens epithelial cells). RESULTS: No significant differences (P>0.05) were found between control and diabetic tissues in their amount of total NAD+ and NADH/retina, and the ratio of NAD+ to NADH, or in their content of lactate, pyruvate, and adenosine triphosphate (ATP) or in the ratio of lactate to pyruvate. The content of lactate and pyruvate in retinas incubated for 2 hours in media containing 10 or 30 mM glucose was the same as found in fresh tissues, but the levels of these metabolites in retinas incubated in media containing 5 mM glucose declined in comparison to the fresh values. There were no significant differences in lactate content in cultured retinal and lens cells that were exposed to 5 or 30 mM glucose-containing media. DISCUSSION: The present results do not support the hyperglycemic pseudohypoxia hypothesis of diabetic retinopathy.
Authors: Michelle A Puchowicz; Kui Xu; Danielle Magness; Casey Miller; W David Lust; Timothy S Kern; Joseph C LaManna Journal: J Cereb Blood Flow Metab Date: 2004-04 Impact factor: 6.200
Authors: Yasuo Ido; Jens R Nyengaard; Kathy Chang; Ronald G Tilton; Charles Kilo; Banavara L Mylari; Peter J Oates; Joseph R Williamson Journal: Antioxid Redox Signal Date: 2010-01 Impact factor: 8.401
Authors: Stefan Haemmig; Ali Hashemi Gheinani; Marina Zaromytidou; Gerasimos Siasos; Ahmet Umit Coskun; Michelle A Cormier; David A Gross; A K M Khyrul Wara; Antonios P Antoniadis; Xinghui Sun; Galina K Sukhova; Fred G P Welt; Ioannis Andreou; Carl Whatling; Li-Ming Gan; Johannes Wikström; Elazer R Edelman; Peter Libby; Peter H Stone; Mark W Feinberg Journal: Arterioscler Thromb Vasc Biol Date: 2021-02-11 Impact factor: 8.311