Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium

PURPOSE. TO evaluate quantitatively the effects of blocking of adhesion mol ecules (P-selectin or intercellular adhesion molecule-1 [ICAM-1]) on leukoc yte dynamics in the retinal microcirculation in vivo during ischemia-reperf usion injury and the therapeutic efficacy of the blocking of adhesion molec ules on retinal ischemia-reperfusion injury. METHODS. Retinal ischemia was induced for 60 minutes in anesthetized pigmen ted rats by temporary ligation of the optic nerve. P-selectin or ICAM-1 mon oclonal antibody (mAb) was administered at 5 minutes before reperfusion. At 4, 12, and 24 hours after onset of reperfusion, leukocyte behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 or 14 days of reperfusion, retinal damage was evalua ted histologically. RESULTS. P-selectin mAb significantly inhibited leukocyte rolling along the major retinal veins after reperfusion. Subsequently, the number of accumul ated leukocytes decreased in the P-selectin-inhibited fats. ICAM-1 mAb also inhibited leukocyte accumulation during the reperfusion period in a more s ubstantial manner than P-selectin mAb. Histologic examination demonstrated the protective effect of the blocking of P-selectin or ICAM-1. In accordanc e with a reduction in leukocyte accumulation, the protective effect of mAb on retinal ischemia-reperfusion injury was more substantial in ICAM-1-inhib ited rats. CONCLUSIONS. The present study demonstrates the inhibitory effect of P-sele ctin and ICAM-1 mAb on leukocyte accumulation and subsequent tissue injury during retinal ischemia-reperfusion injury.