May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Does Hyperglycemia Cause Diabetic Retinopathy ?
Author Affiliations & Notes
  • K.F. LaNoue
    Penn State University, Hershey, PA
    Cellular and Molecular Physiology,
  • M.S. Ola
    Penn State University, Hershey, PA
    Cellular and Molecular Physiology,
  • T.W. Gardner
    Penn State University, Hershey, PA
    Cellular & Molecular Physiology and Ophthalmology,
  • I. Simpson
    Penn State University, Hershey, PA
    Neural and Behavioral Sciences,
  • Footnotes
    Commercial Relationships  K.F. LaNoue, None; M.S. Ola, None; T.W. Gardner, None; I. Simpson, None.
  • Footnotes
    Support  JDRF 4–2002–455, NIH R01 NS38641
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 966. doi:
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      K.F. LaNoue, M.S. Ola, T.W. Gardner, I. Simpson; Does Hyperglycemia Cause Diabetic Retinopathy ? . Invest. Ophthalmol. Vis. Sci. 2006;47(13):966.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Ongoing studies of retinal metabolism in diabetic rats are designed to understand why the retina is damaged by the diabetic state. Diabetic retinopathy is characterized by neuronal apoptic degeneration and impaired blood/retinal barrier properties. Unifying hypothesis to explain these derangements is needed. Can the hyperglycemia, which is characteristic of disease state, explain the pathology?

Methods: : Glucose and glutamate metabolism of excised retinas from 3 weeks and 3 month diabetic rats were studied. Retinas were incubated in 5 mM or 25 mM glucose. We measured glycolysis, 14CO2 production, glutamate synthesis and disposal, polyol formation, lactate/pyruvate ratios, glucose–6–phosphate and fructose–6–phosphate. We also made in vivo measurements of lactate/pyruvate ratios and the sugar phosphates using euglycemic and diabetic rats. Metabolism was rapidly halted in situ via a microwave fixation technique. The activity of glyceraldehyde–3–phosphate dehydrogenase was measured spectrophotometrically.

Results: : One hypothesis suggests that hyperglycemia generates excess reactive oxygen species by flooding the mitochondria with excess reducing equivalents. We measured the influence of hyperglycemia on glycolysis and CO2 production and we found no increase due to high glucose in control or diabetic retinas. Lactate/pyruvate ratios were consistently low and not increased by hyperglycemia. Moreover, the ratio of lactate/pyruvate in the in vivo retinas was similar to those measured in excised retinas. The levels of glucose–6–phosphate and fructose–6–phosphate were similar at high and low glucose in vivo and ex vivo. The fact that rates of glycolysis were slower in diabetic rats was understandable in view of the low activity of glyceraldehyde 3–phosphate dehydrogenase in the diabetic rats. This enzyme is sensitive to oxidative damage. Although glucose metabolism down stream of hexokinase was not influenced by hyperglycemia, upstream glucose metabolism was enhanced. Thus polyol formation from [U14C–glucose] was significantly faster in 25 mM glucose than 5 mM glucose, and at each glucose level, polyol formation was faster in retinas from diabetic rats.

Conclusions: : The retinas of the diabetic rats appear to be damaged by ROS but the ROS are not generated by the mitochondrial electron transfer chain. Current studies are aimed at direct measurements of rates of formation of ROS to identify their source.

Keywords: metabolism • diabetes • mitochondria 

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