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E. C. O'Neill, P. Keane, K. Howell, P. McLoughlin, C. J. O'Brien; The Role of Nitric Oxide in Angiogenesis in the Globally Hypoxic Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3434.
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Vascular endothelial growth factor (VEGF) plays a pivotal role in pathological angiogenesis. This includes the neovascularisation of diabetic retinopathy and other proliferative retinopathies. Hypoxia is a major stimulus for angiogenesis. The actions of vascular endothelial growth factor (VEGF) are known to be in part, mediated by Nitric Oxide (NO). Thus, we investigated the role of NO in hypoxia induced angiogenesis in the mature retina by examining the effect of L-arginine (a NO precursor) on this process.
Adult male Wyster Kyoto rats were housed in normobaric hypoxic conditions (Fi O2 = 0.10) for two weeks. 50% of the group were administered L-arginine (95mmol/l) in their drinking water. The remainder of the animals received no L-arginine. After two weeks they were killed by exsanguination. One eye per animal was cryosectioned and immunostained using endothelial cell marker (isolectin B4). By use of the confocal microscope and stereological techniques endothelial cell size and endothelial cell numbers were assessed.
A significant increase (p<0.05) in endothelial cell number in the ganglion cell layer were found in the hypoxic plus L-arginine (mean +/- SEM: [3.58 +/- 0.11] x 107) when compared to hypoxic alone animals (mean +/- SEM [2.65 +/- 0.07] x 107). A similarly significant increase in endothelial cell numbers was found in the inner retina (p<0.05) and total retina (p<0.05). No significant difference (p>0.05) in endothelial cell size was found between the hypoxia plus L-arginine and the hypoxia alone group.
We concluded that the administration of L-arginine, a NO precursor increased endothelial cell numbers and thus angiogenesis in the globally hypoxic adult retina. Providing more evidence that nitric oxide plays an important role in vascular remodelling during chronic retinal hypoxia. Thus, inhibition of nitric oxide synthase maybe a future treatment option for proliferative retinopathies.
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