Cellular Basis for Bimatoprost Effects on Human Conventional Outflow

Abstract

Taken together, results suggest that bimatoprost specifically activates receptors in both cell types of the human conventional outflow pathway to modify intraocular pressure. However, only TM cell monolayers appear to have autocrine, or agonist-independent, receptor signaling that is sensitive to a prostamide receptor antagonist.

Recent Progress in Prostaglandin F2αEthanolamide (Prostamide F2α) Research and Therapeutics

“…Functional prostamide receptors were found to be present in all cells involved aqueous humor outflow using cellular dielectric spectroscopy. The presence of prostamide receptors on human trabecular meshwork cells was confirmed and, in addition, such receptors were identified on the endothelial cells that line Schlemm's canal (Stamer et al, 2010). These results imply that bimatoprost influences aqueous humor drainage by interacting with both the major cell types that control pressure dependent aqueous humor outflow via the trabecular meshwork.…”

“…These results imply that bimatoprost influences aqueous humor drainage by interacting with both the major cell types that control pressure dependent aqueous humor outflow via the trabecular meshwork. Bimatoprost also increases pressureindependent aqueous humor outflow through the uveoscleral pathway (Richter et al, 2003;Woodward et al, 2010a), and functional prostamide receptors were found to be present on ciliary smooth muscle cells (Stamer et al, 2010). The effects of bimatoprost on trabecular meshwork and endothelial cells of Schlemm's canal were inhibited by the prostamide antagonist AGN 211336 (Wan et al, 2007;Stamer et al, 2010).…”

“…Its ocular hypotensive effects in nonhuman primates involve increased uveoscleral outflow exclusively (Woodward et al, 2010a), but in humans, bimatoprost increases aqueous humor outflow by both the uveoscleral and trabecular meshwork pathways (Brubaker et al, 2001;Christiansen et al, 2004;Lim et al, 2008). The effects of bimatoprost have been examined on the component cells of these two pathways (Wan et al, 2007;Stamer et al, 2010) (see Fig. 2).…”

“…The conventional, pressure dependent pathway via the trabecular meshwork involves both trabecular meshwork cells and the endothelial cells that line Schlemm's canal. By use of the cellular dielectric spectroscopy technique, functional bimatoprost receptors were identified present on both human cell types (Stamer et al, 2010;see Fig. 2).…”

“…Bimatoprost also increases pressureindependent aqueous humor outflow through the uveoscleral pathway (Richter et al, 2003;Woodward et al, 2010a), and functional prostamide receptors were found to be present on ciliary smooth muscle cells (Stamer et al, 2010). The effects of bimatoprost on trabecular meshwork and endothelial cells of Schlemm's canal were inhibited by the prostamide antagonist AGN 211336 (Wan et al, 2007;Stamer et al, 2010). AGN 211336 was also found to abolish the increase in hair growth produced by bimatoprost in isolated human hair follicles (Khidir et al, 2013).…”