title: Effects of a prostaglandin DP receptor agonist, AL-6598, on aqueous humor dynamics in a nonhuman primate model of glaucoma.
abstract: 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 microL 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 microL/min (P = 0.03), and increased aqueous flow from 1.49 +/- 0.10 to 1.93 +/- 0.13 microL/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 PGD(2), 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.
authors.affiliation: Department of Ophthalmology, University of Nebraska Medical Center, Omaha, NE 68198-5840, USA. ctoris@unmc.edu
authors.forename: Carol B
authors.initials: CB
authors.lastname: Toris
authors.forename: Gui-Lin
authors.initials: GL
authors.lastname: Zhan
authors.forename: Michael R
authors.initials: MR
authors.lastname: Feilmeier
authors.forename: Carl B
authors.initials: CB
authors.lastname: Camras
authors.forename: Marsha A
authors.initials: MA
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000502:physiology*; D015237:Dinoprost / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015590:Fluorophotometry; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D011971:Receptors, Immunologic / Q000819:agonists*; D011982:Receptors, Prostaglandin / Q000819:agonists*; D012590:Sclera / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014602:Uvea / Q000187:drug effects / Q000502:physiology
chemical_list: C469387:AL 6598; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015237:Dinoprost; C036293:prostaglandin D2 receptor