Inhibitory effect of ischemic preconditioning on leukocyte participation in retinal ischemia-reperfusion injury

Recent reports have shown that ischemic preconditioning induces strong protection against retinal damage by subsequent prolonged ischemia and that this protection is mediated by mechanisms involving the adenosine A1 receptor. This study was designed to evaluate quantitatively the effects of ischemic preconditioning on leukocyte-mediated reperfusion injury after transient retinal ischemia and to define the role of the adenosine A1 receptor in these effects.

Transient retinal ischemia was induced in male rats by temporary ligation of the optic nerve. Ischemic preconditioning (5 minutes of ischemia) was induced 24 hours before 60 minutes of ischemia. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was administered intramuscularly immediately after ischemic preconditioning. Leukocyte behavior in the retina after 60 minutes of ischemia was evaluated in vivo with acridine orange digital fluorography.

Ischemic preconditioning inhibited leukocyte rolling. The maximum number of rolling leukocytes was reduced to 3.0% at 12 hours after reperfusion (P < 0.01). Subsequent leukocyte accumulation was also decreased with ischemic preconditioning. The maximum number of accumulated leukocytes was reduced to 22.6% at 24 hours after reperfusion (P < 0.01). These inhibitory effects were suppressed by administration of DPCPX (P < 0.0001). The numbers of rolling leukocytes at 12 hours after reperfusion and accumulated leukocytes at 24 hours after reperfusion were 102.7% (NS) and 83.4% (P < 0.01), respectively, compared with the number without ischemic preconditioning.

The present study demonstrates the inhibitory effects of ischemic preconditioning on leukocyte rolling and subsequent leukocyte accumulation during retinal ischemia-reperfusion injury. Furthermore, the adenosine A1 receptor may play an important role in these inhibitory effects.