Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus

Am J Ophthalmol. 2001 Oct;132(4):551-6. doi: 10.1016/s0002-9394(01)01127-8.


Purpose: Inducible nitric oxide synthase has been implicated in the pathogenesis of cerebral ischemic damage, in the angiogenic process and in diabetic vascular damage. This study was undertaken to determine whether inducible nitric oxide synthase is present in the retinas from human subjects with diabetes mellitus.

Methods: This was an experimental immunohistochemical prospective study. Ten postmortem eyes from five subjects with diabetes mellitus, 10 eyes from five subjects without diabetes and without known ocular disease, and two eyes from one subject with unilateral ocular ischemic syndrome secondary to severe carotid artery obstruction were examined. We used immunohistochemical techniques and antibodies directed against inducible nitric oxide synthase, glial fibrillary acidic protein, and vimentin. The main outcome measure was immunoreactivity for these antibodies.

Results: Immunoreactivity for inducible nitric oxide synthase was not observed in retinas from all subjects without diabetes and without ocular disease. Six retinas from three subjects with diabetes and nonproliferative retinopathy, and the retina from the eye with ocular ischemic syndrome showed immunoreactivity for inducible nitric oxide synthase in cells with elongated processes. Based on morphology and on glial fibrillary acidic protein and vimentin immunoreactivity, this inducible nitric oxide synthase immunoreactivity appeared to localize to retinal Müller glial cells.

Conclusions: These observations suggest that Müller cells may be involved in the microvascular remodeling of the diseased retina and that high concentrations of nitric oxide produced by inducible nitric oxide synthase could contribute to neurotoxicity and angiogenesis that occur in diabetic retinopathy.

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 1 / enzymology*
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetic Retinopathy / enzymology*
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Retina / enzymology*
  • Vimentin / metabolism


  • Glial Fibrillary Acidic Protein
  • Vimentin
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II