Local effect of topical FP-receptor agonists on retinal vessels of the ipsilateral posterior retina in normal rabbit eyes

Abstract

To determine whether a topically instilled prostaglandin analogue inhibits endothelin-1 (ET-1)-induced vasoconstrictive effects in the posterior retina by its local effects, and the duration of the effect in normal rabbit eyes. Travoprost, a potent selective FP-agonist, or unoprostone, a prostone that also has a weak non-selective FP-agonistic activity, solution was instilled once, or once daily (travoprost) or twice daily (unoprostone) for 7 days in one randomly chosen Dutch rabbit eye, and vehicle in the contralateral eye. ET-1 was intravitreously injected in both eyes 30 min after a single instillation of a test drug or its vehicle, or just after, 30, 60, 90 or 180 min after the final instillation of a 7-day instillation, and fundus photographed before, 30 and 60 min after the injection to study whether difference was seen in the ET-1-induced constriction of retinal vessels between the drug- and vehicle-instilled eyes. The same experimental procedures were conducted with indomethacin pretreatment. In the rabbit eyes where travoprost was instilled for 7 days, the ET-1-induced constriction of retinal vessels was significantly inhibited only on the drug-treated side, when ET-1 was injected 30 or 60 min after the final instillation (P = 0.026-0.005), which was abolished by indomethacin pretreatment. A single instillation of travoprost or unoprostone and 7-day instillation of unoprostone showed no effect. After a 7-day instillation in normal rabbit eyes, topical travoprost suppressed ET-1-induced vasoconstrictive effects only in the ipsilateral posterior retina by its local effect; this effect was maintained at least for 30 min and mediated by endogenous prostaglandins.