Effects of a prostaglandin DP receptor agonist, AL-6598, on aqueous humor dynamics in a nonhuman primate model of glaucoma

This study examines, in 11 cynomolgus monkeys with unilateral laser-induced glaucoma, the ocular hypotensive mechanism of action of AL-6598, partial agonist at the DP and EP prostanoid receptors. In a crossover fashion, both eyes of each monkey were dosed twice-daily with 25 μL of either AL-6598 0.01% or vehicle for 2 days and on the morning of the 3rd day. Measurements were made on day 3 of each treatment. Alternative treatments were separated by at least 2 weeks. Intraocular pressures (IOPs) were measured by pneumatonometry and aqueous flow and outflow facility by fluorophotometry. Uveoscleral outflow was calculated mathematically. In the normotensive eyes, compared to vehicle treatment, AL-6598 decreased IOP from 22.5 ± 0.7 to 18.7 ± 0.9 mmHg (P = 0.006), increased uveoscleral outflow from 0.47 ± 0.17 to 1.22 ± 0.17 μL/min (P = 0.03), and increased aqueous flow from 1.49 ± 0.10 to 1.93 ± 0.13 μL/min (P = 0.01). No measurement in AL-6598-treated hypertensive eyes was significantly different from vehicle treatment. It is concluded that AL-6598 reduces IOP by increasing uveoscleral outflow in normotensive eyes of ketamine-sedated monkeys, despite an increase in aqueous flow. This effect is different from that of PGD₂, which decreases aqueous flow, and of the selective DP receptor agonist, BW245C, which increases both outflow facility and uveoscleral outflow in addition to decreasing aqueous flow.