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Oscar A Candia, Rosana Gerometta, John Danias; The Use of Tissue Plasminogen Activator to Reduce Elevated Intraocular Pressure Induced by Prednisolone in Sheep.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2884.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown (ARVO 2013) that tissue plasminogen activator (tPA) injected into the vitreous of sheep reduced or prevented the elevation of the intraocular pressure (IOP) normally produced by the instillation of 1% prednisolone. In this presentation we report the effect of tPA when injected into the anterior chamber (AC) in amounts of 0.01, 0.001 and 0.0001 μg diluted in a volume of 50 μL.
Lyophilized tPA, obtained as Actilyse ® 50 mg from Boehringer Ingelheim S.A. (Buenos Aires) containing arginine, was used. Five sheep of the Coriedale breed were selected. Initially all eyes received instillation of 1% prednisolone 3 times/day for 10 days to elevate their IOP from 10 mm Hg to about 23 mm Hg. Then, 0.0001 μg was injected into one of the eyes and its effect was followed for up to 55:00 hrs while the instillation of prednisolone continued in both eyes. The same protocol was implemented for the 0.001 and 0.01 μg amounts (after extended washout) in the contra lateral eyes. 0.423 μg of arginine, which is associated with 0.01 μg tPA, was injected alone and had no effect.
Injection of 0.0001 μg into the AC had no effect on IOP of 23.0 mm Hg at 6:00 and 30:00 hrs after injection. 0.001 μg reduced IOP from 23.1 to 18.6 mm Hg at 6:00 hr but IOP recovered to 22.3 mm Hg at 30:00 hr. Injection of 0.01 μg produced a marked and prolonged reduction of IOP. From a baseline of 23.4, IOP was reduced to 14.2, 19.0, 20.9, and 22.3 mm Hg at 6:00, 30:00, 48:00 and 55:00 hrs, respectively.
Recombinant human tPA is effective in reversing steroid-induced IOP elevation in sheep. The reduction of IOP elevation may be the result of an effect on extra-cellular matrix turnover in the TM. These findings suggest that tPA may be useful as a therapeutic agent in steroid-induced glaucoma.
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