Tacrolimus (FK506) attenuates leukocyte accumulation after transient retinal ischemia.
OBJECTIVE
Tacrolimus, an immunosuppressant agent, has been shown to reduce tissue injury and leukocyte accumulation after transient ischemia. This study was designed to evaluate quantitatively the inhibitory effects of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation in vivo after transient retinal ischemia and the protective effects of tacrolimus on ischemia-induced neural damage.


METHODS
Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic sheath. Tacrolimus was administered at 10 minutes after ischemic induction. At 4, 12, 24, and 48 hours after reperfusion, leukocyte behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 days of reperfusion, ischemia-induced retinal damage was evaluated histologically.


RESULTS
Treatment with tacrolimus suppressed leukocyte rolling; the maximum number of rolling leukocytes was reduced by 60.1% at 12 hours after reperfusion (P<0.05). In tacrolimus-treated rats, the velocity of rolling leukocytes was significantly faster than in vehicle-treated rats (P<0.01). The subsequent leukocyte accumulation was reduced by 61.6% at 24 hours after reperfusion (P<0.01). Histological examination demonstrated the protective effect of tacrolimus on ischemia-induced retinal damage, which was more substantial in the inner retina (P<0.01).


CONCLUSIONS
The present study demonstrated the inhibitory effect of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation and the therapeutic potency to neural injury after transient retinal ischemia.
Tsujikawa
A
A
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan. tujikawa@capricorn.kuhp.kyoto-u.ac.jp
Ogura
Y
Y
Hiroshiba
N
N
Miyamoto
K
K
Kiryu
J
J
Honda
Y
Y
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016559:Tacrolimus