Abstract
Abstract: :
Purpose: Bimatoprost is thought to reduce intraocular pressure (IOP) primarily by increasing uveoscleral outflow. However, recent evidence suggests that bimatoprost may impact conventional outflow as well. Using a cell culture model, the goal of the present study was to determine whether Bimatoprost affects hydraulic conductivity (HC) of trabecular meshwork (TM) and Schlemm’s canal (SC) cell monolayers. Methods: Human TM cells and SC cells were isolated and seeded onto Snapwell filters at confluence according to previously characterized methods. Monolayers were allowed to mature (1–2 weeks for TM and 3 weeks for SC). The cell monolayers were placed into an Ussing–type chamber, exposed to a pressure gradient of 5–10 mm Hg and baseline HC was measured. Cells were treated with bimatoprost (1µM for 30 min.), isoproterenol (1µM for 15 min) or vehicle and HC was measured. Some monolayers were treated with dexamethasone (100 nm for 5 days) and HC compared to paired, vehicle–treated controls. Results: Bimatoprost increased the average HC of TM cell monolayers by 92% (n=5, p<0.01) compared to vehicle control (n=6). For SC cells treated with bimatoprost, the average HC increased by 254% (n=2). In controls for our model system, isoproterenol increased HC by 83% (n=3, p<0.02), while dexamethasone decreased HC by 64.8% (n=3, p<0.01). Conclusions: Results show that bimatoprost interacts with both cell types of the conventional outflow pathway in vitro and suggest that IOP–lowering effects of bimatoprost in vivo may involve both TM and SC cells.
Keywords: outflow: trabecular meshwork • pharmacology • receptors: pharmacology/physiology