Purchase this article with an account.
Panagiotis Laspas, Evgeny Goloborodko, Caroline Manicam, Norbert Pfeiffer, Adrian Gericke; Nitric oxide isoforms and their effect on ophthalmic artery responses and the survival of retinal neurons. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2927.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Disturbances of ocular perfusion have been implicated in the pathophysiology of glaucoma, and nitric oxide (NO) was suggested to be critical in this process. The purpose of the present study was to examine the hypothesis that the lack of one of the three NO synthase (NOS) isoforms, eNOS, iNOS, or nNOS, affects vasodilation responses of ophthalmic arteries and the cell density in the retinal ganglion cell layer of mice.
Three groups of mice with targeted disruption of each of the three NOS genes and respective age-matched wild type controls were used in this study. Intraocular pressure (IOP) was measured in conscious mice by rebound tonometry. Next, mice were killed and ophthalmic arteries were isolated and changes in luminal artery diameter in response to the endothelium-dependent vasodilator acetylcholine and to the NO donor nitroprusside 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.
IOP was similar in eNOS-, iNOS-, or nNOS-deficient mice compared with respective wild type controls. In ophthalmic arteries, acetylcholine and nitroprusside (both 10-9 - 10-4 M) induced concentration-dependent vasodilation that was similar in each of the three NOS knockout genotypes and the wild type mice. The non-isoform-selective NOS inhibitor L-NAME (10-4 M) reduced acetylcholine-induced vasodilation by about 50-70% in all mouse genotypes but in eNOS-deficient mice. In contrast, neither 7-nitroindazole (10-5 M), an inhibitor of nNOS, nor aminoguanidine (3x10-4 M), an iNOS inhibitor, had any effect on acetylcholine-induced vasodilation. The amount of neurons in the retinal ganglion cell layer did not differ between the individual mouse genotypes.
The findings of the study suggest that the lack of a single NOS isoform does not affect endothelium-dependent vasodilation of the ophthalmic artery. Although our studies with NOS inhibitors suggest that eNOS contributes to endothelium-dependent vasodilation, its lack can be compensated functionally probably by NOS-independent vasodilation mechanisms. Furthermore, the lack of a single NOS-isoform does not appear to affect neuron survival in the retinal ganglion cell layer.
This PDF is available to Subscribers Only