Prolonged effect of a new platelet-activating factor antagonist on ocular vascular permeability in an endotoxin model of uveitis

Abstract

Platelet-activating factor (PAF) is a membrane-derived lipid mediator involved in inflammatory responses. In the present study, the effect of a new, synthetic PAF antagonist, BN 50726, on ocular-blood barrier breakdown was investigated in a model of anterior uveitis produced by injection of 5 microL 0.1% endotoxin into the midstroma of rabbit corneas. Severe keratitis and anterior uveitis were induced in 3-4 days. BN 50726 was applied once subconjunctivally and then topically four times daily for 5 days in a blind-designed experiment. Vascular permeability was measured each day with an automated fluorophotometer after injection of fluorescein-conjugated dextran. BN 50726 significantly decreased ocular vascular permeability up to the fifth day of treatment. In another series of animals, slit-lamp observation showed significant reduction in iris erythema and epithelial damage with BN 50726 treatment. These results show that the PAF antagonist reduces early and late responses in uveitis. The possibility that PAF interacts with other inflammatory mediators to affect breakdown of the blood-aqueous barrier is discussed.