Early diabetes-induced biochemical changes in the retina: Comparison of rat and mouse models

I. G. Obrosova, V. R. Drel, A. K. Kumagai, C. Szábo, P. Pacher, M. J. Stevens

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Aims/hypothesis: Recently, various transgenic and knock-out mouse models have become available for studying the pathogenesis of diabetic retinopathy. At the same time, diabetes-induced retinal changes in the wild-type mice remain poorly characterised. The present study compared retinal biochemical changes in rats and mice with similar (6-week) durations of streptozotocin-induced diabetes. Materials and methods: The experiments were performed on Wistar rats and C57Bl6/J mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, α-ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA, and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis. Free mitochondrial and cytosolic NAD+/NADH ratios were calculated from the glutamate and lactate dehydrogenase systems. Results: Retinal glucose concentrations were similarly increased in diabetic rats and mice, vs controls. Diabetic rats manifested ∼26- and 5-fold accumulation of retinal sorbitol and fructose, respectively, whereas elevation of both metabolites in diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and glutathione transferase activities, (3) slightly increased poly(ADP-ribose) immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF protein overexpression. Diabetic mice lacked these changes. SOD activity was 21-fold higher in murine than in rat retinas (the difference increased to 54-fold under diabetic conditions), whereas other antioxidative enzyme activities were 3- to 10-fold lower. With the exception of catalase, the key antioxidant defence enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic rats had decreased free mitochondrial and cytosolic NAD+/NADH ratios, consistent with retinal hypoxia, whereas both ratios remained in the normal range in diabetic mice. Conclusions/interpretation: Mice with short-term streptozotocin-induced diabetes lack many biochemical changes that are clearly manifest in the retina of streptozotocin-diabetic rats. This should be considered when selecting animal models for studying early retinal pathology associated with diabetes.

Original languageEnglish (US)
Pages (from-to)2525-2533
Number of pages9
Issue number10
StatePublished - Oct 2006
Externally publishedYes


  • Mouse
  • NAD/NADH ratio
  • Oxidative stress
  • Poly(ADP-ribosyl)ation
  • Rat
  • Retina
  • Sorbitol pathway of glucose metabolism
  • Streptozotocin diabetes
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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