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Raaya Ezra-Elia, Germana Alegro da Silva, Diogo Sousa Zanoni, Renée Laufer-Amorim, José Luiz Laus, Ron Ofri; Sildenafil does not prevent retinal damage in a rat model of acute ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2416.
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© ARVO (1962-2015); The Authors (2016-present)
Loss of vision in glaucoma is due to progressive death of retinal ganglion cells (RGCs) and their axons. Mounting evidence suggests that reduced blood flow in the inner retina and optic nerve might play a role in the pathogenesis of glaucomatous neuropathy. Nitric oxide (NO) is known to increase blood flow by decreasing vascular resistance in ocular circulation. Consequently, impaired NO synthesis and release are considered potential pathogenic factors in glaucomatous neuropathy of some patients. Based on results in different organs, we hypothesized that sildenafil, a phosphodiesterase inhibitor which prolongs the effect of NO, may be neuroprotective. To test this hypothesis we evaluated sildenafil treatment in a rat model of acute ocular hypertension.
Anterior chamber cannulation was performed to induce acute intraocular pressure (IOP) elevation for 60 minute duration in one randomly-chosen eye of 38 Lewis rats. Twenty rats received sildenafil (0.5 mg/kg, n=9) or saline (n=11) intraperitoneally for seven days. Eighteen rats received double dose of sildenafil (1 mg/kg, n=9) or saline (n=9) intraperitoneally for 18 days. Treatment began three days before IOP elevation. Full-field electroretinography (ERG) recordings were conducted using both dark- and light-adapted protocols. Seven days prior to IOP elevation RGCs were retrogradely labeled by bilateral stereotaxic injection of fluorogold and counted following retinal flatmount preparation.
Mean ±SE IOP of cannulated eyes was 70.1 ±1.5 mmHg. ERG confirmed significant functional deficits in hypertensive eyes compared with fellow un-cannulated eyes of saline-treated animals under both scotopic and photopic conditions, thus validating the cannulation model. No significant functional differences were observed between sildenafil- and saline-treated animals when comparing the ERG a- and b-wave amplitudes and implicit time ratios of hypertensive and fellow eyes in either of the experimental groups. RGC counts were also significantly lower in hypertensive eyes compared with fellow un-cannulated eyes, and no differences were observed between sildenafil- and saline-treated animals.
Both RGC counts and ERG failed to show any (prophylactic or therapeutic) neuroprotective effect of sildenafil in a rat acute ocular hypertension model, implying that treatment may not be beneficial for glaucoma patients.
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