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Oscar Candia, Rosana Gerometta, John Danias; Reduction by tissue plasminogen activator (tPA) of steroid-induced intraocular pressure (IOP) elevation in sheep. Invest. Ophthalmol. Vis. Sci. 2013;54(15):769. doi: https://doi.org/.
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To determine whether human recombinant tPA can reduce steroid-induced IOP elevation.
Eight sheep of the Corriedale breed were treated with drops of 1% prednisolone acetate 3-times a day in both eyes. After the expected IOP increase, the animals received 100-mL intravitreal injections in one eye of human recombinant tPA containing 100, 200, 500 and 1000 mg concentrations dissolved in BSS (two animals for each concentration). IOP was monitored for 19 more days while the animals continued to receive treatment with prednisolone. Periodic slit lamp examination was also performed.
Treatment with prednisolone for 10 days increased mean (+SD) IOP to 24.1(+1.6) mmHg from a baseline of 10.2(+1.1) mmHg (p<0.00001, t-test). Treatment with tPA decreased IOP within 24h for all doses tested to 14.1(+1.1) mmHg which was significantly lower than that of the contralateral uninjected eye for all animals (p<0.00003, paired t-test). The effect was evident for all tPA doses, independent of the dose (p>0.05, ANOVA) and lasted for 19 days at which time IOP in the two eyes became similar (p>0.05). Transient conjunctival injection and corneal clouding were observed in some eyes, but were unrelated to the dose injected and cleared up in all eyes within 48 hrs.
tPA decreases IOP, probably by affecting extracellular matrix turnover in the TM. This finding may have therapeutic implications in glaucoma.
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