Time course of NADH oxidase, inducible nitric oxide synthase and peroxynitrite in diabetic retinopathy in the BBZ/Wor rat

E. Ann Ellis, Dennis L. Guberski, Brenda Hutson, Maria B. Grant

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64 Scopus citations

Abstract

This study investigated the time course of NADH oxidase, a source of superoxide in the vascular endothelium, inducible nitric oxide synthase (iNOS), and peroxynitrite (ONOO-) in the BBZ/Wor rat, a spontaneous model of noninsulin dependent diabetes (NIDDM). Colloidal gold-labeled immunocytochemical studies of iNOS and nitrotyrosine, a marker for OONO-, were done on sections of retinas from male BBZ/Wor rats in which NADH oxidase was localized by cerium derived cytochemistry at three time points: prediabetes (prior to the onset of hyperglycemia); new onset diabetes (2-6 days after onset of hyperglycemia); and chronic diabetes (4-18 months after onset of hyperglycemia). Control retinas were from age matched non-diabetic BBDR/Wor rats. The percentage of blood vessels positive for NADH oxidase increased significantly (P = 0.05) in new onset (64.2 ± 6.5%) and chronic diabetes (83.2 ± 11.4%), as compared to prediabetes (25.8 ± 5.6%) and nondiabetic controls (33.6 ± 15.9%). The percentage of blood vessels positive for iNOS immunoreactivity was significantly higher in new onset diabetic retinas (69.6 ± 5.88%, P = 0.0001; 8.9 ± 3.29 colloidal gold particles (cgp)/50 μm2) than in chronic diabetic retinas (49.9 ± 9.75%; 7.9 ± 5.12 cgp) and both were significantly higher (P = 0.0001) than in prediabetic (3.7 ± 0.81%; 0.4 ± 0.56 cgp) and nondiabetic control retinas (8.7 ± 4.66%; 1.2 ± 1.40 cgp). In new onset diabetes, levels of nitrotyrosine immunoreactivity (60.8 ± 16.91 cgp) were significantly higher (P = 0.0001) than those in chronic diabetes (29.5 ± 4.31 cgp); both were significantly higher (P = 0.0001) than those in prediabetic (8.2 ± 1.70 cgp) and nondiabetic retinas (9.0 ± 1.87 cgp). There was no cumulative increase in nitrotyrosine in the chronic diabetic retinas as a function of time. In rats with diabetes there was disruption of the inner blood-retinal barrier. These results suggest that iNOS and ONOO- may contribute to retinal damage in diabetes from the onset of hyperglycemia in NIDDM.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalNitric Oxide - Biology and Chemistry
Volume6
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • Diabetes
  • Inducible nitric oxide synthase
  • Nitrotyrosine
  • Oxidative stress
  • Peroxynitrite
  • Retinopathy

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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