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S.S. Samudre, D. Tibbs, F.A. Lattanzio, Jr, R.C. Allen, I. Castillo, P. Loose–Thurman, E.R. Crouch, Jr; Chronic Application of Topical WIN 55–212–2 in a Rat Glaucoma Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3784.
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Synthetic and naturally occuring cannabinoids are known to decrease intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. The purpose of this study is to determine if the decrease in IOP is maintained during chronic topical application of WIN 55–212–2 (WIN) without adverse systemic or ocular effects.
The rat glaucoma model was created in six Sprague–Dawley rats by ligating 3 of 4 episcleral veins of the right eye using 9.0 silk sutures. Within 6 wk, IOP increased by at least 5 mm Hg in the operated eye, measured via Goldmann tonometry under sedation. IOP, heart rate, and blood pressure were measured weekly. Baseline measurements and confocal microscopy were performed 3 d prior to administration of WIN (dissolved in TocrisolveTM) and repeated at week 5, i.e. 1 week after the last day of drug administration. The right eye was treated topically three times per day with either 20 µl of WIN (0.5 %) or TocrisolveTM alone for 4 weeks and then the rats allowed to recover without drug treatment before the final measurements on week 5.
Baseline IOP was 14.1 ± 0.6 mmHg in the operated eye; BP = 134±8/98±8 mm Hg; HR = 349±30 BPM. WIN, 0.5%, decreased IOP (p<0.001) but had no effect on BP or HR. The trend towards IOP decline in the contralateral eye was not significant (p=0.15). TocrisolveTM alone had no effect on IOP. The cornea, conjunctiva and anterior chamber were normal with no signs of ocular inflammation.
In an ocular hypertensive model topically applied WIN is an effective and non–toxic ocular hypotensive agent. The effect was maximum after two weeks treatment with possible involvement of the contralateral eye. IOP returned to baseline after the drug was discontinued. There were no effects on HR or BP, such as those associated with systemic administration. Longer term experiments are necessary to determine if the IOP reduction can be maintained and if WIN will decrease glaucomatous retinal damage.
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