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B'Ann T. Gabelt, Galen H. Heyne, Julie A. Kiland, Paul L. Kaufman; Effect of Nitric Oxide on Ocular Physiology in the Cynomolgus Monkey. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1526. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on intraocular pressure (IOP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF) and outflow facility (OF) in cynomolgus monkeys.
IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophometry, blood pressure with a cuff. Following baseline (BL) measurements, eyes were treated with single or multiple topical treatments with 500µg SNP or L-NAME, to one eye, vehicle (PBS) to the opposite eye. OF by two-level constant pressure perfusion was determined for 45-60 min at BL and after each anterior chamber exchange with 10-5 M SNP followed by 10-4 M SNP (n=5) or 10-5 M L-NAME followed by 10-4 M L-NAME (n=2) to one eye; Bárány’s perfusand to the contralateral eye. Following OF determination with L-NAME, monkeys were euthanized. Frozen sections of the anterior segment were stained for NADPH-diaphorase to indicate NOS activity.
Following topical treatment at 4x30 min intervals with 500µg SNP/treatment, IOP was significantly decreased from 2-6 hr compared to the contralateral control after correction for pretreatment baseline (approx. 20mmHg), with the maximum IOP lowering at 3hr (20% reduction, p<0.001, n=8). PD, rfx, and mean arterial pressure (MAP) were unchanged. AHF measurements at 30 min intervals from 0.5-4 hr post SNP treatment will be reported. OF after SNP exchange was unchanged compared to vehicle control after correction for baseline. Topical L-NAME (2x30 min intervals with 500µg/treatment, n=8) had no effect on IOP, PD, rfx or MAP. NADPH-d staining was qualitatively no different in anterior segments from eyes perfused with L-NAME vs vehicle control. OF results following L-NAME were inconclusive with n=2.
The nitric oxide donor, SNP, was effective in lowering IOP following repeated topical administration at short intervals. The mechanism for the IOP lowering is under investigation. The inhibition of NOS activity by L-NAME was not confirmed by NADPH-d staining although these are the same concentrations utilized to inhibit NOS in studies conducted in other species. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.
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