Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice

S. E. Brooks, X. Gu, S. Samuel, D. M. Marcus, M. Bartoli, P. L. Huang, R. B. Caldwell

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

Purpose. Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)-derived oxidants such as peroxynitrate and tested this hypothesis in a mouse model of ROP. Methods. Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor NGnitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. Results. Oxygen-induced retinal vaso-obliteration was significantly reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso-obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. Conclusions. These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number1
StatePublished - Jan 30 2001

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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