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S. C. Coons, Z. Wan, D. F. Woodward, W. D. Stamer; Bimatoprost and AGN211334 Effects on Hydraulic Conductivity of Trabecular Monolayers. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3923. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The goal of the present study was to investigate the effects of bimatoprost and a novel prostamide-selective antagonist, AGN 211334, on hydraulic conductivity of human trabecular meshwork cell monolayers.
Drug effects on hydraulic conductivity (HC) were tested across mature human trabecular meshwork (TM) cell monolayers cultured on polycarbonate filters. Cells were mounted in an Ussing-like chamber, exposed to a 10mmHg pressure head on their apical side, and hydraulic conductivity was recorded continuously during 30 minute intervals.
Exposure of TM cell monolayers to bimatoprost (1µM), increased HC by 78±25%, (p<0.01, n=9) above baseline measurements. Pretreatment or co-treatment of cells with AGN 211334 (30µM) significantly antagonized bimatoprost effects (n=6-17, p<0.01). Interestingly, AGN 211334 exposure alone decreased HC across cell monolayers by 51±0.8% (p<0.01, n=17). As a positive control, isoproterenol (1µM) increased HC by 78.7±21% (p<0.01, n=11). Isoproterenol, in combination with bimatoprost, increased HC by 51.7±15.5% (n=10).
Bimatoprost increases flow across TM monolayers in a receptor-dependent manner that was antagonized by AGN 211334. By itself, AGN 211334 appeared to inhibit endogenous signaling that decreased baseline HC. Interestingly, the mechanism of action of bimatoprost and isoproterenol appear similar due to a lack of additivity when exposed to TM monolayers together.
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