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Adrian Gericke, Caroline Manicam, Mayagozel B Zhutdieva, Panagiotis Laspas, Norbert Pfeiffer; Role of Oxidative Stress on Endothelium-Dependent Vasodilation in the Ophthalmic Artery and on Retinal Ganglion Cell Survival in Mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4352.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress is known to impair vascular function and has been implicated in the pathophysiology of glaucoma. The goal of the present study was to test the hypothesis that oxidative stress impairs endothelium-dependent vasodilation in the ophthalmic artery and reduces retinal ganglion cell (RGC) density in mice.
Apolipoprotein E-deficient (ApoE-/-) mice, a model of oxidative stress, and respective wild type controls were studied at the age of 12 months (n=8 per genotype). Intraocular pressure (IOP) was measured in conscious mice by rebound tonometry. After mice had been killed by CO2 inhalation, ophthalmic arteries were isolated and changes in luminal artery diameter in response to the endothelium-dependent vasodilator acetylcholine were measured using video microscopy. Moreover, retinal wholemounts were prepared and stained using cresyl violet in order to evaluate the number of neurons in the retinal ganglion cell layer, and optic nerve cross-sections were cut and stained with toluidine blue in order to determine the number of axons in the optic nerve.
IOP was similar in ApoE-/- and wild type mice. Acetylcholine (10-9 - 10-4 M) induced concentration-dependent vasodilation that did not differ between ApoE-/- and wild type mice. While the non-isoform-selective nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10-4 M) reduced acetylcholine-induced vasodilation by about 50% in wild type mice, it only minimally affected responses in ApoE-/- mice. Addition of 30 mM KCl abolished acetylcholine-induced vasodilation, indicative of the involvement of hyperpolarizing factors (EDHFs). Neither the neuron number in the retinal ganglion cell layer nor the axon number in the optic nerve differed between ApoE-/- and wild type mice.
Our data suggest, that in murine ophthalmic arteries, oxidative stress reduces the contribution of nitric oxide to endothelium-dependent dilation, but the vasodilation responses appear to be completely retained by EDHFs. The data also suggest that oxidative stress does not affect RGC number.
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