Early diabetes-induced biochemical changes in the retina

Comparison of rat and mouse models

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

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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
JournalDiabetologia
Volume49
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Retina
NAD
Poly Adenosine Diphosphate Ribose
Experimental Diabetes Mellitus
Sorbitol
Fructose
Vascular Endothelial Growth Factor A
Glutamic Acid
Glucose
Proteins
Glutathione Reductase
Diabetic Retinopathy
Enzymes
Streptozocin
Glutathione Peroxidase
Glutathione Transferase
Malondialdehyde
Pyruvic Acid
L-Lactate Dehydrogenase
Ammonia

Keywords

  • 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

Cite this

Obrosova, I. G., Drel, V. R., Kumagai, A. K., Szabo, C., Pacher, P., & Stevens, M. J. (2006). Early diabetes-induced biochemical changes in the retina: Comparison of rat and mouse models. Diabetologia, 49(10), 2525-2533. https://doi.org/10.1007/s00125-006-0356-7

Early diabetes-induced biochemical changes in the retina : Comparison of rat and mouse models. / Obrosova, I. G.; Drel, V. R.; Kumagai, A. K.; Szabo, Csaba; Pacher, P.; Stevens, M. J.

In: Diabetologia, Vol. 49, No. 10, 10.2006, p. 2525-2533.

Research output: Contribution to journalArticle

Obrosova, IG, Drel, VR, Kumagai, AK, Szabo, C, Pacher, P & Stevens, MJ 2006, 'Early diabetes-induced biochemical changes in the retina: Comparison of rat and mouse models', Diabetologia, vol. 49, no. 10, pp. 2525-2533. https://doi.org/10.1007/s00125-006-0356-7
Obrosova, I. G. ; Drel, V. R. ; Kumagai, A. K. ; Szabo, Csaba ; Pacher, P. ; Stevens, M. J. / Early diabetes-induced biochemical changes in the retina : Comparison of rat and mouse models. In: Diabetologia. 2006 ; Vol. 49, No. 10. pp. 2525-2533.
@article{474a3d8559f24a1dacdfed17e0f86f7c,
title = "Early diabetes-induced biochemical changes in the retina: Comparison of rat and mouse models",
abstract = "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.",
keywords = "Mouse, NAD/NADH ratio, Oxidative stress, Poly(ADP-ribosyl)ation, Rat, Retina, Sorbitol pathway of glucose metabolism, Streptozotocin diabetes, Vascular endothelial growth factor",
author = "Obrosova, {I. G.} and Drel, {V. R.} and Kumagai, {A. K.} and Csaba Szabo and P. Pacher and Stevens, {M. J.}",
year = "2006",
month = "10",
doi = "10.1007/s00125-006-0356-7",
language = "English (US)",
volume = "49",
pages = "2525--2533",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - Early diabetes-induced biochemical changes in the retina

T2 - Comparison of rat and mouse models

AU - Obrosova, I. G.

AU - Drel, V. R.

AU - Kumagai, A. K.

AU - Szabo, Csaba

AU - Pacher, P.

AU - Stevens, M. J.

PY - 2006/10

Y1 - 2006/10

N2 - 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.

AB - 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.

KW - Mouse

KW - NAD/NADH ratio

KW - Oxidative stress

KW - Poly(ADP-ribosyl)ation

KW - Rat

KW - Retina

KW - Sorbitol pathway of glucose metabolism

KW - Streptozotocin diabetes

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=33748516742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748516742&partnerID=8YFLogxK

U2 - 10.1007/s00125-006-0356-7

DO - 10.1007/s00125-006-0356-7

M3 - Article

VL - 49

SP - 2525

EP - 2533

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -