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I.–H. Pang, D.L. Fleenor, P.E. Hellberg, A.F. Clark; Propentofylline Stimulation of Trabecular Meshwork Stromelysin–1 (MMP–3) and Increase in Aqueous Outflow Facility . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4429.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:. Elevated intraocular pressure in primary open angle glaucoma is associated with the deposition of extracellular matrix material in the outflow pathway and increased aqueous outflow resistance. In an effort to identify new agents that may alter glaucomatous changes to the trabecular meshwork (TM), we have tested the neuroprotective agent propentofylline (PPF) for its effect on TM cell stromelysin–1 (MMP–3) expression and for its effect on aqueous outflow in perfusion cultured human anterior segments. Methods: Cultured human TM cells were treated with PPF (100 µM) for 24–72 hours and media levels of proMMP–3 were measured by ELISA. The effect of PPF on aqueous outflow was determined in perfusion cultured human anterior segments under constant pressure, variable flow conditions. Results: Treatment of cultured human TM cells with PPF for 72 h significantly increased proMMP–3 expression by 229 ± 19% (mean ± SEM, n = 47, p<0.001). PPF (100 µM) significantly (p < 0.05) enhanced outflow facility by 20–30% at 1–3 days after treatment in human anterior segments perfused under constant pressure. PPF also significantly increased proMMP–3 concentration in the perfusate of days 1 and 3 by 20–40% after the initiation of treatment (p < 0.05). Conclusion:. PPF stimulates human TM cell MMP–3 expression and increases aqueous humor outflow facility. These results suggest that PPF may be a new IOP–lowering agent. [Supported by Alcon Research, Ltd.]
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