Document Detail

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes.
MedLine Citation:
PMID:  17583794     Owner:  NLM     Status:  MEDLINE    
AIMS/HYPOTHESIS: Diabetes results in the upregulation of the production of several components of the inflammatory response in the retina, including inducible nitric oxide synthase (iNOS). The aim of this study was to investigate the role of iNOS in the pathogenesis of the early stages of diabetic retinopathy using iNOS-deficient mice (iNos (-/-)). MATERIALS AND METHODS: iNos (-/-) mice and wild-type (WT; C57BL/6J) mice were made diabetic with streptozotocin or kept as non-diabetic controls. Mice were killed at different time points after the induction of diabetes for assessment of vascular histopathology, cell loss in the ganglion cell layer (GCL), retinal thickness, and biochemical and physiological abnormalities. RESULTS: The concentrations of nitric oxide, nitration of proteins, poly(ADP-ribose) (PAR)-modified proteins, endothelial nitric oxide synthase, prostaglandin E(2), superoxide and leucostasis were significantly (p < 0.05) increased in retinas of WT mice diabetic for 2 months compared with non-diabetic WT mice. All of these abnormalities except PAR-modified proteins in retinas were inhibited (p < 0.05) in diabetic iNos (-/-) mice. The number of acellular capillaries and pericyte ghosts was significantly increased in retinas from WT mice diabetic for 9 months compared with non-diabetic WT controls, these increases being significantly inhibited in diabetic iNos (-/-) mice (p < 0.05 for all). Retinas from WT diabetic mice were significantly thinner than those from their non-diabetic controls, whereas diabetic iNos (-/-) mice were protected from this abnormality. We found no evidence of cell loss in the GCL of diabetic WT or iNos (-/-) mice. Deletion of iNos had no beneficial effect on diabetes-induced abnormalities on the electroretinogram. CONCLUSIONS/INTERPRETATION: We demonstrate that the inflammatory enzyme iNOS plays an important role in the pathogenesis of vascular lesions characteristic of the early stages of diabetic retinopathy in mice.
L Zheng; Y Du; C Miller; R A Gubitosi-Klug; S Ball; B A Berkowitz; T S Kern
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-06-22
Journal Detail:
Title:  Diabetologia     Volume:  50     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-07     Completed Date:  2008-01-07     Revised Date:  2008-01-14    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1987-96     Citation Subset:  IM    
Department of Medicine, 448B Biomedical Research Building, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
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MeSH Terms
Capillaries / enzymology*
Diabetes Mellitus, Experimental / enzymology,  pathology*
Diabetic Retinopathy / enzymology*
Dinoprostone / blood
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / deficiency,  metabolism*
Reference Values
Retina / metabolism
Retinal Degeneration / enzymology*
Retinal Vessels / enzymology*
Superoxides / metabolism
Grant Support
Reg. No./Substance:
10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 363-24-6/Dinoprostone; EC Oxide Synthase Type II
Erratum In:
Diabetologia. 2007 Oct;50(10):2228

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