Inhibitory effects of thrombin inhibitor on postischemic leukocyte–endothelial cell interactions in the retina

Abstract

Abstract: : Purpose: Thrombin inhibitors have been shown to suppress neural injury after transient cerebral ischemia. It has also been reported that the neuroprotective effect is due to an anticoagulant function. The current study was designed to evaluate quantitatively the inhibitory effects of thrombin inhibitor on leukocyte–endothelial cell interactions after transient retinal ischemia. Methods: Retinal ischemia was induced for 60 minutes in Long–Evans rats by temporary ligation of the optic sheath. Argatroban, a selective thrombin inhibitor, was administered just after induction of ischemia. Leukocyte behavior in the retinal microcirculation was then evaluated in vivo with acridine orange leukocyte fluorography. The expressions of P–selectin and intercellular adhesion molecule–1 (ICAM–1) were evaluated with reverse transcription polymerase chain reaction. After 10 days of reperfusion, ischemia–induced retinal damage was assessed histologically. Results: Treatment with argatroban attenuated leukocyte–endothelial cell interactions; the maximum numbers of rolling and accumulated leukocytes were reduced by 89.6% (P<0.05) and 58.2% (P<0.05), respectively, at 12 hours after reperfusion. The expressions of P–selectin and ICAM–1 mRNA were suppressed significantly in the argatroban–treated retinas (P<0.01). Histologic examination showed the significant protective effect of argatroban on ischemia–induced retinal damage (P<0.01). Conclusions: Treatment with argatroban attenuated leukocyte–endothelial cell interactions after transient retinal ischemia. This inhibitory effect on postischemic blood cell–endothelial cell interactions might contribute to its neuroprotective effects.

Keywords: retina • ischemia • drug toxicity/drug effects