Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy

Anusha Mishra, Eric A. Newman

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Neuronal activity leads to arteriole dilation and increased blood flow in retinal vessels. This response, termed functional hyperemia, is diminished in the retinas of diabetic patients, possibly contributing to the development of diabetic retinopathy. The mechanism responsible for this loss is unknown. Here we show that light-evoked arteriole dilation was reduced by 58% in a streptozotocin-induced rat model of type 1 diabetes. Functional hyperemia is believed to be mediated by glial cells and we found that glialevoked vasodilation was reduced by 60% in diabetic animals. The diabetic retinas showed neither a decrease in the thickness of the retinal layers nor an increase in neuronal loss, although signs of early glial reactivity and an upregulation of inducible nitric oxide synthase (iNOS) were detected. Inhibition of iNOS restored both light- and glial-evoked dilations to control levels. These findings suggest that high NO levels resulting from iNOS upregulation alters glial control of vessel diameter and may underlie the loss of functional hyperemia observed in diabetic retinopathy. Restoring functional hyperemia by iNOS inhibition may limit the progression of retinopathy in diabetic patients.

Original languageEnglish (US)
Pages (from-to)1996-2004
Number of pages9
JournalGLIA
Volume58
Issue number16
DOIs
StatePublished - Dec 2010
Externally publishedYes

Fingerprint

Hyperemia
Nitric Oxide Synthase Type II
Diabetic Retinopathy
Neuroglia
Dilatation
Arterioles
Retina
Up-Regulation
Light
Retinal Vessels
Streptozocin
Type 1 Diabetes Mellitus
Vasodilation

Keywords

  • Diabetes
  • GLIAL cells
  • INOS
  • Neurovascular coupling
  • Retina

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy. / Mishra, Anusha; Newman, Eric A.

In: GLIA, Vol. 58, No. 16, 12.2010, p. 1996-2004.

Research output: Contribution to journalArticle

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