Prostaglandin-independent inhibition of ocular vascular permeability by a platelet-activating factor antagonist.
Platelet-activating factor (PAF), a lipid mediator of inflammation, may markedly increase vascular permeability. We assessed the ability of the PAF antagonist SRI 63-441 to inhibit ocular vascular permeability induced by the intravenous injection of endotoxin or anterior chamber paracentesis. The PAF antagonist SRI 63-441 significantly blocked ocular vascular permeability following either intravenous endotoxin or anterior chamber paracentesis as determined by the reduction in accumulation of 70,000-molecular-weight fluorescein isothiocyanate-conjugated dextran or serum proteins into the anterior chamber. SRI 63-441 did not reduce increases in aqueous humor prostaglandin E2 levels. The efficacy of the PAF antagonist was additive in combination with either topical indomethacin or topical corticosteroid. Combined therapy almost completely prevented increases in ocular vascular permeability. These data support the conclusion that multiple mediators contribute to ocular vascular permeability and that combinations of pharmacologic agents may be superior to a single drug.
Rubin
R M
RM
Oregon Health Sciences University, Portland 97201.
Samples
J R
JR
Rosenbaum
J T
JT
D000818:Animals; D000867:Anterior Chamber; D001082:Aqueous Humor / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D004357:Drug Synergism; D009877:Endophthalmitis / Q000378:metabolism / Q000503:physiopathology; D004731:Endotoxins; D005123:Eye / Q000098:blood supply* / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D011458:Prostaglandins E / Q000378:metabolism; D011677:Punctures; D011806:Quinolinium Compounds / Q000494:pharmacology*; D011817:Rabbits
D004731:Endotoxins; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D011806:Quinolinium Compounds; C050531:SRI 63-441; D003907:Dexamethasone; D015232:Dinoprostone; D007213:Indomethacin