Protective effects of selectin ligands/inhibitor (SKK-60060) against retinal ischemia-reperfusion injury

被引:17
作者
Matsubara, A
Tomida, K
Matsuda, Y
Tamai, K
Tashita, A
Jomori, T
Tsujikawa, A
Ogura, Y
机构
[1] Nagoya City Univ, Sch Med, Dept Ophthalmol, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan
关键词
leukocytes; selectin; ischemia-reperfusion injury; microcirculation; retina; selectin inhibitor;
D O I
10.1006/exer.2000.0880
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
A newly developed selectin ligand inhibitor (SKK-60060) has been shown to block P- and L-selectins in vitro. We examined its inhibition of leukocyte-endothelial interactions in vivo against retinal ischemia-reperfusion injury and protective effects on ischemia-induced retinal damage. Retinal ischemia was induced by temporary ligation of the optic sheath for 60 min in anesthetized pigmented rats. SKK-60060 was administered 5 min before reperfusion and 4, 12, 24 and 48 hr thereafter, and leukocyte dynamics in the retinal microcirculation were evaluated using acridine orange digital fluorography. After 7 days of reperfusion, ischemia-induced retinal damage was also assessed histologically. SKK-60060 treatment suppressed leukocyte rolling during the reperfusion period: their numbers in the SKK-60060-treated rats were reduced by 67.0% (P < 0.01) and 53.2% (P < 0.01) at 12 and 24 hr, respectively. The subsequent leukocyte accumulation was also inhibited in SKK-60060-treated rats: accumulated leukocytes in the SKK-60060-treated rats were reduced by 72.8% (P < 0.01) and 53.4% (P < 0.01) at 12 and 24 hr, respectively. Retinal venous vasodilation in SKK-60060-treated rats were significantly suppressed at each time point (P < 0.05). Histological examination demonstrated protective effects of SKK-60060 on ischemia-induced retinal damage, which were more substantial in the inner retina (P < 0.01). SKK-60060 significantly inhibits the leukocyte rolling along the major retinal veins and their accumulation during the reperfusion period. These results suggest therapeutic potential of SKK-60060 for ischemia-reperfusion injury. (C) 2000 Academic Press.
引用
收藏
页码:283 / 293
页数:11
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