Retinal ischemia-reperfusion injury attenuated by blocking of adhesion molecules of vascular endothelium.
OBJECTIVE
To evaluate quantitatively the effects of blocking of adhesion molecules (P-selectin or intercellular adhesion molecule-1 [ICAM-1]) on leukocyte dynamics in the retinal microcirculation in vivo during ischemia-reperfusion injury and the therapeutic efficacy of the blocking of adhesion molecules on retinal ischemia-reperfusion injury.


METHODS
Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic nerve. P-selectin or ICAM-1 monoclonal 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 evaluated histologically.


RESULTS
P-selectin mAb significantly inhibited leukocyte rolling along the major retinal veins after reperfusion. Subsequently, the number of accumulated leukocytes decreased in the P-selectin-inhibited rats. ICAM-1 mAb also inhibited leukocyte accumulation during the reperfusion period in a more substantial manner than P-selectin mAb. Histologic examination demonstrated the protective effect of the blocking of P-selectin or ICAM-1. In accordance with a reduction in leukocyte accumulation, the protective effect of mAb on retinal ischemia-reperfusion injury was more substantial in ICAM-1-inhibited rats.


CONCLUSIONS
The present study demonstrates the inhibitory effect of P-selectin and ICAM-1 mAb on leukocyte accumulation and subsequent tissue injury during retinal ischemia-reperfusion injury.
Tsujikawa
A
A
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Ogura
Y
Y
Hiroshiba
N
N
Miyamoto
K
K
Kiryu
J
J
Tojo
S J
SJ
Miyasaka
M
M
Honda
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology*; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000473:pathology*; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012171:Retinal Vessels
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1