Abnormalities of retinal metabolism in diabetes or experimental galactosemia VIII. Prevention by aminoguanidine

Curr Eye Res. 2000 Oct;21(4):814-9. doi: 10.1076/ceyr.21.4.814.5545.


Purpose: Aminoguanidine has been found to inhibit the development of some retinal lesions in diabetic rats and diabetic dogs, thereby raising a possibility that the formation of glycation end products (AGEs) may be an essential step in the pathogenesis of the retinopathy. The purpose of this study is to investigate the effect of aminoguanidine administration on other metabolic abnormalities which might be involved in the development of retinopathy in two models of the retinopathy, alloxan diabetes and experimental galactosemia.

Methods: Oxidative stress, nitric oxide (NO) and the activity of protein kinase C (PKC, total activity) were measured in the retina of the rats experimentally diabetic or galactosemic for 2 months. Effect of aminoguanidine administration on the inhibition of hyperglycemia-induced retinal dysmetabolism was investigated.

Results: Two months of diabetes or experimental galactosemia in rats resulted in elevation of retinal oxidative stress (increase in thiobarbituric acid reactive substances, TBARS, and decrease in glutathione, GSH), NO, and PKC activity. Aminoguanidine supplementation (2.5 g aminoguanidine/kg rat diet) significantly inhibited each of these abnormalities in retinas of diabetic rats and galactosemic rats, and did so without lowering the blood hexose levels of these animals.

Conclusions: The ability of aminoguanidine to normalize the hyperglycemia-induced increases in retinal oxidative stress, NO and PKC in diabetic rats and galactose-fed rats suggests that these abnormalities may be inter-related in the retina, and that the biochemical mechanism by which aminoguanidine inhibits retinal microvascular disease in diabetes may be complex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / prevention & control*
  • Diet
  • Galactosemias / complications
  • Galactosemias / metabolism*
  • Glutathione / metabolism
  • Guanidines / administration & dosage*
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Oxidative Stress / drug effects*
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / metabolism*
  • Thiobarbituric Acid Reactive Substances / metabolism


  • Guanidines
  • Thiobarbituric Acid Reactive Substances
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Protein Kinase C
  • Glutathione
  • pimagedine