Aqueous Humor Dynamics in Monkeys After Topical R(+)–DOI

Abstract

Abstract: : Purpose: To determine the effects of R(+)–DOI, a selective 5–HT₂ agonist, on intraocular pressure (IOP) and aqueous humor dynamics in monkeys. Methods: Normotensive cynomolgus monkeys were treated topically once daily with 4x5µl 0.5% R(+)–DOI (n=8) to one eye, vehicle to the opposite eye. 6 hour IOP response (Goldmann) and slit lamp examination (SLE) were determined prior to dosing and on the 3^rd day of treatment. Aqueous humor formation (AHF) was determined by fluorophotometry encompassing hours 3–8 after the 3^rd dose (n=8). In another group of monkeys (n=8), beginning 3.5 hr after the 4^th or 5^th dose, AHF was measured by dilution of radio–iodinated monkey albumin (I–MSA) perfused through the anterior chamber, and flow to blood (FTB) by accumulation of I–MSA in the general circulation. Uveoscleral outflow (Fu) = AHF – FTB. FTB was determined at both spontaneous and elevated pressures allowing calculation of trabecular outflow facility (Ctrab). Total outflow facility (Ctot) was determined at the conclusion of the isotope measurements by two–level constant pressure perfusion. Results:IOP lowering in treated (T) eyes was compared to the opposite control (C) eyes corrected for the 6 hour IOP baseline prior to the first dose. Following the 3^rd dose of 0.5% R(+)–DOI (4x5µl) IOP was significantly (p<0.01, n=7) decreased by 1.4–4.7 mmHg over the 6 hrs (pretreatment IOP = 15.0±0.4mmHg). AHF (fluoro) was increased by 16±6% (p<0.025) in T compared to C eyes post–treatment corrected for baseline. Isotope dilution showed that AHF increased by 30% (p<0.01), FTB decreased by 28% and Fu increased by 241% (p<0.05). Ctot and Ctrab were unchanged. Conclusions:R(+)–DOI, a selective 5–HT₂ agonist, causes a small but significant increase in AHF, and lowers IOP in normotensive monkeys primarily by increasing Fu.

Keywords: intraocular pressure • outflow: ciliary muscle • outflow: trabecular meshwork