dinoprost and Uveitis--Anterior

Muramyl dipeptide (MDP) (N -acetylmuramyl- L -alanyl- D - isoglutamine) was injected intracamerally to test if MDP applied to the aqueous side of the blood-aqueous barrier would increase paracellular permeability in association with diminished uptake of glutamate. The symptoms of anterior uveitis, i.e., increase in vascular dilatation, could be detected as early as 30 min post MDP injection while aqueous protein concentration did not increase at this time suggesting an initial dissociation between the circulatory and epithelial barrier responses. However, at 45 min, the aqueous protein concentration increased 10-fold (201+/-174 to 2094+/-1835 micrograms ml-1;P<0.001) rising progressively to 20-fold above the control eye at 60 min post injection (254+/-194 vs. 5038+/-2514 micrograms ml-1;P<0.001). Epithelial cell barrier paracellular permeability increased at 45 min as evidenced by the enhanced efflux of radiolabelled L -glucose out of the aqueous (8% and 13% faster than control at 45 and 60 min post MDP injection, respectively), coinciding with the accelerated protein influx. A near 50% reduction in efflux of both radiolabelled glutamate and D -aspartate was consistent with reduced glutamate uptake by the transport system X-AG. In addition, a 24% decline in aqueous glutamate, but not aspartate, was detected in the aqueous of the MDP-treated eyes in association with a 54% decrease in iris/ciliary body gamma-glutamyltranspeptidase activity consistent with reduced de novo glutamate formation from glutamine. The aqueous of MDP injected eyes also had 6-fold and 34-fold higher prostaglandin E2and F2alphaconcentrations, respectively (P

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Amino Acid Transport System X-AG; Animals; Aqueous Humor; ATP-Binding Cassette Transporters; Bicarbonates; Biological Transport; Blood-Aqueous Barrier; Dinoprost; Dinoprostone; Eye Proteins; gamma-Glutamyltransferase; Glucose; Intraocular Pressure; Permeability; Rabbits; Uveitis, Anterior

In this study the effect of topical administration of prostaglandins (PGs) on a human serum albumin (HSA)-induced uveitis is evaluated. Topical prostaglandin E1 (PGE1) and prostaglandin F2 alpha (PGF2 alpha) partly inhibited hyperaemia and flare in the anterior chamber after the induction of immune complex uveitis. A marked increase in the cellular response was observed in the aqueous humour after topical PGE1 and PGF2 alpha. Topical prostaglandins may decrease endogenous prostaglandin formation and reduce the prostaglandin-mediated inflammatory symptoms; on the other hand, they also stimulate the aqueous cellular response, possibly by facilitation of leukotriene formation. These results indicate that topical prostaglandins should not be used to treat immunogenic uveitis.

Topics: Administration, Topical; Alprostadil; Animals; Antigen-Antibody Reactions; Aqueous Humor; Conjunctiva; Dinoprost; Disease Models, Animal; Drug Evaluation, Preclinical; Hyperemia; Prostaglandins E; Rabbits; Serum Albumin; Uveitis, Anterior