TACROLIMUS (FK506) ATTENUATES LEUKOCYTE ACCUMULATION AFTER TRANSIENT RETINAL ISCHEMIA

Background and Purpose-Tacrolimus, an immunosuppressant agent, has bee n shown to reduce tissue injury and leukocyte accumulation after trans ient ischemia. This study was designed to evaluate quantitatively the inhibitory effects of tacrolimus on leukocyte rolling and on subsequen t leukocyte accumulation in vivo after transient retinal ischemia and the protective effects of tacrolimus on ischemia-induced neural damage . Methods-Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic sheath. Tacrolimus w as administered at 10 minutes after ischemic induction. At 4, 12, 24, and 48 hours after reperfusion, leukocyte behavior in the retinal micr ocirculation was evaluated in vivo with acridine orange digital fluoro graphy. After 7 days of reperfusion, ischemia-induced retinal damage w as evaluated histologically. Results-Treatment with tacrolimus suppres sed leukocyte rolling; the maximum number of rolling leukocytes was re duced by 60.1% at 12 hours after reperfusion (P<0.05). In tacrolimus-t reated rats, the velocity of rolling leukocytes was significantly fast er than in vehicle-treated rats (P<0.01). The subsequent leukocyte acc umulation was reduced by 61.6% at 24 hours after reperfusion (P<0.01). Histological examination demonstrated the protective effect of tacrol imus on ischemia-induced retinal damage, which was more substantial in the inner retina (P<0.01), Conclusions-The present study demonstrated the inhibitory effect of tacrolimus on leukocyte rolling and on subse quent leukocyte accumulation and the therapeutic potency to neural inj ury after transient retinal ischemia.