Published Online
on July 17, 2003

A more recent version of this article appeared on August 1, 2003

This Article Full Text (PDF) All Versions of this Article: 34/8/2043    most recent 01.STR.0000083052.01361.3Dv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miyahara, S. Articles by Honda, Y. Search for Related Content PubMed PubMed Citation Articles by Miyahara, S. Articles by Honda, Y. Related Collections Acute Cerebral Infarction Pathology of Stroke Anticoagulants Antiplatelets Transient Ischemic Attacks

Submitted on March 20, 2003
Accepted on April 15, 2003

Argatroban Attenuates Leukocyte- and Platelet-Endothelial Cell Interactions After Transient Retinal Ischemia

Shinsuke Miyahara MD; Junichi Kiryu MD^*; Akitaka Tsujikawa MD; Hideto Katsuta MD; Kazuaki Nishijima MD; Kazuaki Miyamoto MD; Kenji Yamashiro MD; Atsushi Nonaka MD; and Yoshihito Honda MD

From the Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

^* To whom correspondence should be addressed. E-mail: kiryu{at}kuhp.kyoto-u.ac.jp.

Background and Purpose--Argatroban, a direct thrombin inhibitor, has been shown to reduce neural injury after transient cerebral ischemia. It has also been reported that this neuroprotective effect results from an anticoagulant function. This study was designed to evaluate quantitatively the inhibitory effects of argatroban on leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

Methods--Retinal ischemia was induced for 60 minutes in male Long-Evans rats by temporary ligation of the optic sheath (n=342). Argatroban was administered just after induction of ischemia. Leukocyte and platelet behavior in the retinal microcirculation was then evaluated in vivo with scanning laser ophthalmoscopy. The expression of P-selectin and intracellular adhesion molecule-1 (ICAM-1) was evaluated by reverse transcription-polymerase chain reaction. After 10 days of reperfusion, ischemia-induced retinal damage was evaluated histologically.

Results--Treatment with argatroban suppressed leukocyte-endothelial cell interactions; the maximum numbers of rolling and accumulated leukocytes were reduced by 90.1% (P<0.05) and 58.7% (P<0.05), respectively, at 12 hours after reperfusion. Treatment with argatroban also suppressed platelet-endothelial cell interactions; the maximum numbers of rolling and adhering platelets were reduced by 91.8% (P<0.01) and 78.9% (P<0.01), respectively, at 12 hours after reperfusion. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P<0.01). Histologic examination demonstrated the protective effect of argatroban on ischemia-induced retinal damage (P<0.01).

Conclusions--Argatroban treatment suppressed leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia. This inhibitory effect on postischemic blood cell-endothelial cell interactions might partially contribute to its neuroprotective effects.

Key words: ischemia • leukocytes • platelets • retina • rheology

This article has been cited by other articles:

				M. Hollborn, C. Petto, A. Steffen, S. Trettner, A. Bendig, P. Wiedemann, A. Bringmann, and L. Kohen Effects of Thrombin on RPE Cells Are Mediated by Transactivation of Growth Factor Receptors Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4452 - 4459. [Abstract] [Full Text] [PDF]

				S. Miyahara, L. Almulki, K. Noda, T. Nakazawa, T. Hisatomi, S. Nakao, K. L. Thomas, A. Schering, S. Zandi, S. Frimmel, et al. In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis FASEB J, June 1, 2008; 22(6): 1973 - 1980. [Abstract] [Full Text] [PDF]

				H Tamura, J Kiryu, K Miyamoto, K Nishijima, H Katsuta, S Miyahara, F Hirose, Y Honda, and N Yoshimura In vivo evaluation of ocular inflammatory responses in experimental diabetes Br J Ophthalmol, August 1, 2005; 89(8): 1052 - 1057. [Abstract] [Full Text] [PDF]

				K. Musashi, J. Kiryu, K. Miyamoto, S. Miyahara, H. Katsuta, H. Tamura, F. Hirose, and N. Yoshimura Thrombin Inhibitor Reduces Leukocyte-Endothelial Cell Interactions and Vascular Leakage after Scatter Laser Photocoagulation Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2561 - 2566. [Abstract] [Full Text] [PDF]

				S. Miyahara, J. Kiryu, K. Miyamoto, H. Katsuta, F. Hirose, H. Tamura, K. Musashi, Y. Honda, and N. Yoshimura In Vivo Three-Dimensional Evaluation of Leukocyte Behavior in Retinal Microcirculation of Mice Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 4197 - 4201. [Abstract] [Full Text] [PDF]

				S. Miyahara, J. Kiryu, K. Yamashiro, K. Miyamoto, F. Hirose, H. Tamura, H. Katsuta, K. Nishijima, A. Tsujikawa, and Y. Honda Simvastatin Inhibits Leukocyte Accumulation and Vascular Permeability in the Retinas of Rats with Streptozotocin-Induced Diabetes Am. J. Pathol., May 1, 2004; 164(5): 1697 - 1706. [Abstract] [Full Text] [PDF]

				F. Hirose, J. Kiryu, K. Miyamoto, K. Nishijima, S. Miyahara, H. Katsuta, H. Tamura, and Y. Honda In Vivo Evaluation of Retinal Injury After Transient Ischemia in Hypertensive Rats Hypertension, May 1, 2004; 43(5): 1098 - 1102. [Abstract] [Full Text] [PDF]