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J.E. Brady, P. McLoughlin, C.J. O'Brien; The Effect of Nitric Oxide Synthase Inhibition on Angiogenesis in the Globally Hypoxic Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2593.
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Angiogenesis plays a pathological role in the constellation of disorders known as the proliferative retinopathies. Although the response of endothelial cells to hypoxia and resultant retinal neovascularization has been extensively studied, most research to date has occurred using an immature circulation. However there are disparities in developmental and adult neovascularization. We examined the role of the Vascular Endothelial Growth Factor– Nitric Oxide Synthase molecular pathway in retinal neovascularization using a novel in vivo model utilizing the effect of global hypoxia in mature animals.
Adult Male Sprague Dawley rats (n=5 in each group) were housed in a normobaric hypoxic chamber for two weeks and exposed to a fraction of inspired oxygen (FiO2) of 0.10. A treatment group received L–NAME – a nitric oxide synthase inhibitor at a dose of 2g/l via drinking water while control animals were maintained in hypoxic conditions for the same duration. After two weeks they were killed by exsanguination. One eye per animal was cryosectioned and immunostained using an endothelial cell marker (GSL B4 lectin). Slides were examined with a confocal microscope and stereological techniques used to assess volume of the retinal vasculature
There was a statistically significant (p<0.05) difference in volume density of retinal vasculature within the ganglion cell layer.
We conclude that inhibition of nitric oxide synthase leads to a significant inhibition of vascular remodeling within the context of a chronic hypoxic stimulus. These results reinforce the potential of the global hypoxia model as a credible alternative in vivo approach utilizing a mature circulation and also demonstrate the permissive role of nitric oxide synthase in ocular neovascularisation
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