Histological protection against ischemia-reperfusion injury by early ischemic preconditioning in rat retina.
Brief ischemia was reported to protect various cells against injury induced by subsequent ischemia-reperfusion, and this phenomenon is known as ischemic preconditioning. The aims of the present study were to clarify whether early ischemic preconditioning could be observed in the rat retina by histological examination. Male Sprague-Dawley rats were subjected to 60 min of retinal ischemia by raising intraocular pressure to 130 mm Hg. Ischemic preconditioning was achieved by applying 5 min of ischemia 5-60 min before 60 min of ischemia. Additional groups of rats received 10 mg/kg 8-phenyltheophiline and 4.5 mg/kg 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), adenosine A1 receptor antagonists, 5 mg/kg 5-hydroxydecanoate and 1 mg/kg glibenclamide, ATP-sensitive K+ channel blockers, or 2.5 mg/kg chelerythrine and 0.1 mg/kg bisindolylmaleimide I, protein kinase C inhibitors, 15 or 30 min before preconditioning. In the non-preconditioned group, cell loss in the ganglion cell layer and thinning of the inner plexiform and inner nuclear layer were observed 7 days after 60 min of ischemia. Five minutes of preconditioning ischemia 20-40 min before 60 min of sustained ischemia completely prevented the retinal tissue damage induced by the sustained ischemia. Treatment with 8-phenyltheophylline, DPCPX, 5-hydroxydecanoate, glibenclamide, chelerythrine and bisindolylmaleimide I almost completely reduced the protective effect of early ischemic preconditioning. The results in the present study indicated that early ischemic preconditioning was demonstrated in the rat retina. Stimulation of adenosine receptors, opening of ATP-sensitive K+ channels and activation of protein kinase C might be involved in the underlying protective mechanisms.
Sakamoto
Kenji
K
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 9-1 Shirokane 5-chome, Minato, Tokyo 108-8641, Japan. sakamotok@pharm.kitasato-u.ac.jp
Yonoki
Yuzuru
Y
Kuwagata
Mayumi
M
Saito
Maki
M
Nakahara
Tsutomu
T
Ishii
Kunio
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007429:Intraocular Pressure / Q000502:physiology; D007511:Ischemia / Q000473:pathology*; D019194:Ischemic Preconditioning; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012171:Retinal Vessels; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline