NADPH diaphorase activity in the rat retina during the early stages of experimental diabetes

Qing Li, Esther Zemel, Benjamin Miller, Ido Perlman

Research output: Contribution to journalArticlepeer-review


Background: Nitric oxide (NO) plays an important physiological role in inter-cellular communication, but when produced in excess it can become toxic. Our goal was to evaluate possible involvement of NO in the development of retinopathy in diabetic rats. Methods: Diabetes was induced in male albino rats by intravenous injection of streptozotocin. Some of the normal and diabetic rats were raised with added L-arginine to increase in vivo NO synthesis, or with added L-NAME to inhibit the rate of in vivo NO synthesis. NADPH diaphorase histochemistry was conducted on retinal whole mounts and transverse sections at different time intervals after induction of diabetes. The electroretinogram (ERG) was recorded to assess retinal function. Results: After 6 weeks of diabetes, NADPH diaphorase amacrine cells in the diabetic retinas appeared abnormal in their morphology and the degree of staining was decreased in their processes. In contrast, NADPH diaphorase activity was augmented in Müller cells. Supplementing the rats' diet with L-arginine for 10 weeks slightly reduced NADPH diaphorase activity in amacrine cell in normal rats but had no effect on the diabetic rats. Adding L-NAME for 10 weeks did not alter NADPH diaphorase histochemistry in either normal or diabetic rats. The ERG responses were reduced by L-arginine supplementation in normal and diabetic rats, and were unaffected by adding L-NAME to the drinking water. Conclusions: Our findings are consistent with the hypothesis that high glucose levels are deleterious to the rat retina and that excessive synthesis of NO may contribute to the development of diabetic retinopathy.

Original languageEnglish
Pages (from-to)747-756
Number of pages10
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Issue number9
StatePublished - 1 Sep 2003
Externally publishedYes


  • Amacrine cells
  • Diabetes
  • Electroretinogram
  • Müller cells
  • Nitric oxide
  • Rat
  • Retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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