Protective effects of selectin ligands/inhibitor (SKK-60060) against retinal ischemia-reperfusion injury.
A newly developed selSep;71(3)28 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.
Matsubara
A
A
Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan. matubara@med.nagoya-cu.ac.jp
Tomida
K
K
Matsuda
Y
Y
Tamai
K
K
Tashita
A
A
Jomori
T
T
Tsujikawa
A
A
Ogura
Y
Y
D000818:Animals; D004187:Disaccharides / Q000627:therapeutic use*; D004727:Endothelium / Q000502:physiology; D019041:L-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology; D019007:P-Selectin / Q000502:physiology*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology
D004187:Disaccharides; D019007:P-Selectin; C414367:SKK 60060; D019041:L-Selectin