Abstract
The effects of bimatoprost on aqueous humor dynamics were quantified in monkey eyes. Uveoscleral outflow was measured by the anterior chamber perfusion method, using FITC-dextran. Total outflow facility was determined by the two-level constant pressure method. Aqueous flow was measured with a scanning ocular fluorophotometer. Uveoscleral outflow was 0.96 ± 0.19 μL min−1 in vehicle-treated eyes and 1.37 ± 0.27 μL min−1 (n = 6; P < .05) in eyes that received bimatoprost 0.01% b.i.d. × 5 days. Bimatoprost had no effect on total outflow facility, which was 0.42 ± 0.05 μL min−1 at baseline and 0.42 ± 0.04 μL min−1 after bimatoprost treatment. Bimatoprost had no significant effect on aqueous humor flow. This study demonstrates that bimatoprost increases uveoscleral outflow but not total outflow facility or aqueous humor flow, indicating that it lowers intraocular pressure in ocular normotensive monkeys by a mechanism that exclusively involves uveoscleral outflow.
Highlights
Bimatoprost (Lumigan) is a highly efficacious ocular hypotensive agent, [1,2,3,4,5] with a unique pharmacology [1]. It mimics the activity of the prostaglandin ethanolamides, which are formed from the endocannabinoid anandamide by cyclo-oxygenase-2 (COX-2) [6,7,8,9]
Several studies have demonstrated that the pharmacology of the prostamides and bimatoprost is distinct from that of the prostaglandins [1, 10,11,12,13,14,15,16] and the endocannabinoids [17]
The differentiated pharmacology of bimatoprost is manifest in the clinical setting where it lowers intraocular pressure (IOP) in open-angle glaucoma and ocular hypertensive patients who are nonresponders to the FP receptor agonist prodrug latanoprost [18,19,20]
Summary
Bimatoprost (Lumigan) is a highly efficacious ocular hypotensive agent, [1,2,3,4,5] with a unique pharmacology [1]. It mimics the activity of the prostaglandin ethanolamides (prostamides), which are formed from the endocannabinoid anandamide by cyclo-oxygenase-2 (COX-2) [6,7,8,9]. Measurement of uveoscleral outflow in patients, of necessity, is derived indirectly. It is calculated from measurements of aqueous humor flow, outflow facility, and an assumed typical value for episcleral venous pressure.
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