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(Investigative Ophthalmology and Visual Science. 2005;46:2561-2566.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.04-1102
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Thrombin Inhibitor Reduces Leukocyte–Endothelial Cell Interactions and Vascular Leakage after Scatter Laser Photocoagulation

Kunihiro Musashi, Junichi Kiryu, Kazuaki Miyamoto, Shinsuke Miyahara, Hideto Katsuta, Hiroshi Tamura, Fumitaka Hirose, and Nagahisa Yoshimura

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

PURPOSE. Macular edema is one of the most serious adverse effects after retinal scatter laser photocoagulation. It has been suggested that the inflammatory reaction after photocoagulation may be involved in the pathogenesis of macular edema. This study was designed to evaluate quantitatively the inhibitory effects of argatroban, a direct thrombin inhibitor, on leukocyte–endothelial cell interactions and vascular permeability after scatter laser photocoagulation.

METHODS. Argon laser photocoagulation was performed in one half of the retina in pigmented male rats (n = 114). Argatroban was administered just before scatter laser photocoagulation. In the other half of the retina, AO leukocyte fluorography was used to evaluate in vivo leukocyte rolling along the retinal vein and accumulation in the retinal capillary bed. The expressions of P-selectin and intercellular adhesion molecule (ICAM)-1 were evaluated by reverse transcription–polymerase chain reaction. Retinal vessel permeability was quantified by using fluorescein isothiocyanate (FITC)-conjugated dextran.

RESULTS. Scatter laser photocoagulation caused significant inflammatory leukocyte–endothelial cell interactions in the nonphotocoagulated half of the retina. Treatment with argatroban suppressed leukocyte–endothelial cell interactions. The maximum number of rolling and accumulating leukocytes was reduced by 46.6% (P < 0.01) and 51.4% (P < 0.01), respectively. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P < 0.05). Retinal vascular permeability was also suppressed significantly (P < 0.05).

CONCLUSIONS. Argatroban suppressed leukocyte–endothelial cell interactions and blood–retinal barrier breakdown after scatter laser photocoagulation, suggesting that argatroban prevents postlaser macular edema.






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