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Francesco Impagnatiello, Barbara Giambene, Francesca Fabrizi, Elena Bastia, Fernando Galassi, Emanuela Masini; The NO donor, isorbide-5-mononitrate alone or combined with timolol, latanoprost or dorzolamide ameliorates intraocular pressure and ocular hemodynamic in an experimental model of glaucoma in rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4449.
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Ocular hypertension is the major risk factor in glaucoma. However, other risk factors of vascular origin have been identified. Nitric oxide (NO) signalling seems to play a crucial role, being involved in the regulation of aqueous humour (AH) outflow and ocular hemodynamics. We studied the effects on intraocular pressure (IOP) and retrobulbar hemodynamic following 28 days daily topical dosing with isosorbide-5-mononitrate (ISMN, 0.5%), either alone or combined with the β-blocker, timolol (0.5%), the prostaglandin F2α agonist, latanoprost (0.05%) and the carbonic anhydrase inhibitor, dorzolamide (2%) in an experimental rabbit model of glaucoma.
Ocular hypertension was obtained by the injection of carbomer (0.1%, 0.1ml) in the anterior chamber of New Zealand White rabbits. IOP was measured using a Tono-Pen. Retrobulbar hemodynamics of the ophthalmic artery was assessed using Color Doppler Imaging. The examinations were performed prior to drug treatment (baseline) and 7, 14, 21 and 28 days thereafter. Furthermore, cGMP content in AH was monitored throughout the experimental period to address the extent of NO signalling pathway activation.
On average, IOP rose from 13.4±2.0 mmHg at baseline to 38.9±4.0 mmHg one week post carbomer injection and remained stable thereafter. Timolol, latanoprost, and dorzolamide lowered IOP (on average 20-30%, p<0.001) at all time points post dose. ISMN, albeit less effectively, also lowered IOP in this model and the effect was additive when co-administered with timolol, latanoprost or dorzolamide. Similarly, carbomer increased the resistivity index of the ophthalmic artery from 0.48±0.02 (basal) to 0.62±0.03 (one week post carbomer, p<0.05). ISMN reversed this effect when administered alone or combined with timolol, latanoprost or dorzolamide. Consistent with the above findings, NO markers i.e. cGMP and nitrate were increased in AH following ISMN treatment.
ISMN by re-establishing physiologic NO signaling in target ocular tissues, ameliorates the effects of current treatments on IOP and ocular hemodynamics.
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