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P.A. Keane, C. O'Brien, P. McLoughlin; The Role of the Nitric Oxide Precursor, L–Arginine in Angiogenesis Involving the Globally Hypoxic Adult Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4184.
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Abnormal blood vessel formation (neovascularization) is the characteristic feature of a number of retinal disorders and these are known as the proliferative retinopathies. Neovascularization in the mature retinal circulation occurs predominantly due to angiogenesis. The major stimulus for the angiogenic processes is retinal tissue hypoxia. We induced angiogenesis in a murine model of the mature retinal circulation and then investigated the role of nitric oxide in this process by administering the nitric oxide precursor L–arginine.
16 Adult male Wystar Kyoto rats were exposed to hypoxic conditions (FiO2=0.10) for two weeks. Half the rats formed a treatment group and received L–arginine (95mmol/L) in their water supply while the other half formed a control group and did not. Using stereological techniques, a significant increase (p<0.05, unpaired t–test) was found in the volume density of blood vessels in the ganglion cell layer in the treatment group (mean+/–SEM: 31.1+/– 1.8%) compared with the control group (21.3+/–1.8%). A trend towards an increase (p=0.06, unpaired t–test) was seen in the volume of blood vessels in the ganglion cell layer in the treatment group (3.8x10–3 +/– 0.0 ml) compared with the control group (2.1x10–3 +/– 0.0 ml).
We conclude that the administration of the nitric oxide precursor, L–arginine leads to vascular remodelling in the mature retinal circulation of hypoxic rats. These findings provide more evidence of the essential role that nitric oxide plays in retinal angiogenesis.
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