Effect of WEB 2086-BS, an antagonist of platelet-activating factor receptors, on retinal vascularity in diabetic rats

Specific antagonists of platelet-activating factor (PAF) receptors inhibit platelet aggregation and thromboxane synthesis. These two processes have been implicated in the course of diabetic retinopathy. We assessed the effect of a specific PAF receptor antagonist, WEB 2086-BS (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f) (1,2,4 triazolo-(4,3-a(1 P)-diazepine-2-yl)-1-(4-morpholinyl)-1-propanone) on retinal vascularity in a model of experimental streptozocin-induced diabetes in rats. Rats were divided into five experimental groups (10 animals/group): group I, non-diabetic group LI, untreated diabetic group LII, diabetic given 1 mg/kg per day of WEB 2086-BS (p.o.) group IV, diabetic given 5 mg/kg per day (p.o.) and group V, diabetic given 10 mg/kg per day (p.o.). After 3-month treatment, platelet aggregometry, platelet synthesis of thromboxane B-2, aortic production of 6-keto-prostaglandin F-1 alpha, platelet and vascular lipid peroxidation, and percentage of the retinal area occupied by horseradish peroxidase-labeled vessels were measured. Untreated diabetic rats showed an increase in platelet reactivity, reduced 6-keto-prostaglandin F-1 alpha production, increased thromboxane B-2 and lipid peroxides, and a decrease in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels. WEB 2086-BS produced a decrease in platelet aggregation induced by collagen in whole blood, in thromboxane B-2 synthesis and Lipid peroxide production, and an increase in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels (13.9 +/-: 1.1% in group II and 9.9 +/- 0.8% in group V). There was a statistically significant linear correlation (Y = -0.72 + 137X, r(2) = 0.7247, P < 0.0007) between thromboxane B-2 values and the percentages of retinal area occupied by horseradish peroxidase-labeled vessels in the groups of animals treated with WEB 2086-BS. (C) 1998 Elsevier Science B.V. All rights reserved.