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Pierre-Paul Elena, Nicolas Cimbolini, Sophie Antonelli, Marielle Bouzin, Laurence Feraille, Karen Viaud, Marie-Françoise Nicolas, Stéphanie Laurent, Christian Blot; Comparison of the effect of Dexamethasone and Prednisolone Acetate in a rat model of glucocorticoid-induced ocular hypertension following topical delivery. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2001. doi: https://doi.org/.
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The ocular use of glucocorticoids (GCs) is often accompanied by an elevation of intraocular pressure (IOP) that can lead to secondary glaucoma. In the search for new selective GC receptor modulators, this side-effect represents a major challenge in drug discovery because of the lack of standardized animal models to assess GC-increased IOP. A number of models are available but are replete with conflicting results, produce low IOP variation, or are not easily accessible and quite expensive. The purpose of the study was to validate a rat model of GC-induced ocular hypertension using two GCs with strong (dexamethasone, DXM) and weaker (prednisolone acetate, PA) anti-inflammatory potency.
Sprague-Dawley rats (n=10/group) were randomized on baseline IOP values, allocated in three groups and topically treated for 5 weeks on both eyes with saline solution (four times a day, 20 µL/eye), 1% PA (four times a day, 10 µL/eye) or 0.1% DXM (twice a day, 20 µL/eye). IOP was measured once weekly in both eyes with a tonometer. It was assessed at the same time in the morning to avoid circadian variations, 0.5 to 1.5 h after the first ocular administration of the day. Body weights were recorded once weekly and thymus (an immune tissue sensitive to GC exposure) was weighted at sacrifice in all animals.
IOP increased through the 5 weeks of dosing to raise mean IOP values of 16.9 ± 3.2 and 15.8 ± 3.3 mm Hg on day 28 and 15.9 ± 2.1 and 15.6 ± 2.7 mm Hg on day 35 in the PA and DXM groups, respectively. The mean IOP values in vehicle group increase from 8.2 ± 0.8 to 10.2 ± 1.6 mm Hg in the same period. Body weight gain vs. control group was significantly decreased in PA-treated groups whilst abolished by DEX during the dosing phase; thymus weights were similarly and dramatically reduced in all GC-treated animals.
In this rat model of GC-induced ocular hypertension, daily ocular instillations of 1% PA or 0.1% DXM produced significant and similar IOP increases up to 6-7 mm Hg over controls. The activity of these two GCs with different anti-inflammatory potency indicates that this model can be particularly useful to assess new GC receptor modulators and to study molecular mechanisms responsible for GC-induced ocular hypertension and primary open-angle glaucoma.
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