Aqueous Humor Dynamics in Monkeys after Topical R-DOI

Abstract

To determine the effects of R-DOI, a selective 5-HT2 agonist, on intraocular pressure (IOP) and aqueous humor dynamics in monkeys. Normotensive cynomolgus monkeys (n = 8) were treated topically once daily with four 5-muL drops of 0.5% R-DOI in one eye, vehicle in the opposite eye. The 6-hour IOP response (Goldmann applanation tonometry) was determined before the drug application and on the third day of treatment. Aqueous humor formation, or flow (AHF, measured by fluorophotometry), was measured from hours 3 to 8 after the third dose. Beginning 3.5 hours after the fourth or fifth dose, AHF was measured by dilution of radio-iodinated monkey albumin perfused through the anterior chamber and flow to blood by accumulation of albumin in the general circulation. Uveoscleral outflow (Fu) was calculated. Flow to blood was determined at spontaneous and elevated pressures, allowing calculation of trabecular outflow facility. Total outflow facility was determined by two-level constant pressure perfusion from 3.5 to 5 hours and from 5.5 to 6.25 hours after R-DOI treatment. Reduction of IOP in treated eyes was compared to the opposite control eyes corrected for the 6-hour IOP baseline before the first dose. After the third dose of R-DOI, IOP was significantly (P < 0.01, n = 7) decreased by 1.4 to 4.7 mm Hg over the 6 hours. AHF (by fluorophotometry) increased by 13% (P < 0.05, n = 8) in treated compared with control eyes corrected for baseline. AHF (isotope dilution) increased by 30% (P < 0.01, n = 8), flow to blood decreased by 28% (n = 5), and Fu increased by 241% (P < 0.05, n = 5). Total and trabecular outflow facility were unchanged. R-DOI caused a small but significant increase in AHF and lowered IOP in normotensive monkeys primarily by increasing Fu.