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Shaily Shah, Sandeep Kumar, Terete Borras, Matthew Smith, John Danias; Effect of Tissue Plasminogen Activator on Outflow Facility of Steroid Injected Mouse Eyes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):788.
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To determine whether over-expression of the tissue plasminogen activator (PLAT) gene can increase outflow facility in a mouse model of steroid-induced glaucoma
Adenoviral vectors carrying cDNA of the sheep PLAT gene and a fluorescent reporter gene (mCherry) (AdPLAT) or with no transgene (AdNull) were created. Transgene expression was driven by the CMV promoter. 3 groups of C57/B6 mice received either: 1. 20µl of triamcinolone acetonide (TA) suspension (40mg/ml) subconjunctivally bilaterally followed immediately by unilateral intracameral injection with 2µl AdPLAT (3-4x1012 VG/ml) 2. 20µl TA subconjunctivally bilaterally followed one week later by unilateral intracameral injection with 2µl AdPLAT 3. 20µl TA subconjunctivally bilaterally followed immediately by bilateral injection with 2µl AdNull IOP was measured preterminally. Outflow facility was determined using simultaneous pressure and flow measurements. After outflow facility measurement, all AdPLAT injected eyes were dissected and viewed under a fluorescent microscope to inspect for mCherry expression in the trabecular meshwork (TM). Eyes that showed mCherry expression were analyzed as a separate group from eyes that showed minimal mCherry expression.
IOP was not significantly different between all eye groups (p>0.05) after either one or two weeks of treatment with TA. Eyes subjected to one week of TA treatment that showed mCherry/PLAT expression had 63%, 54%, and 31% higher outflow facility than AdPLAT treated eyes with minimal mCherry/PLAT expression, contralateral control eyes, and AdNull treated eyes respectively (ANOVA, p<0.05). Eyes subjected to two weeks of TA treatment that showed mCherry/PLAT expression had 86% and 58% higher outflow facility than AdPLAT treated eyes with minimal mCherry/PLAT expression and contralateral control eyes respectively (ANOVA, p<0.05).
Treatment with AdPLAT can both prevent and reverse the decrease in outflow facility caused by steroid treatment in mice.
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