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Cornea:
doi: 10.1097/ICO.0b013e31823f8b9c
Basic Investigation

Inhibition of Corneal Neovascularization in Rats by Systemic Administration of Sorafenib

Seo, Jeong Won MD*; Chung, So-Hyang MD, PhD†,‡; Choi, Jun-Sub PhD; Joo, Choun-Ki MD, PhD†,‡

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Abstract

Purpose: To evaluate the effect of orally administered sorafenib on corneal neovascularization in rat models.

Methods: In male Sprague-Dawley rats, a silver nitrate applicator was placed on the central cornea in both eyes to elicit angiogenesis. Rats were divided into 3 groups, the control group and the 2 sorafenib-treated groups (low dose, 30 mg·kg−1·day−1; high dose, 60 mg·kg−1·day−1). The area of corneal neovascularization was measured by image analysis. Vascular endothelial growth factor receptor 2 (VEGFR2) messenger RNA expression was measured in rat corneas by reverse transcription–polymerase chain reaction, and the expression of phosphorylated extracellular signal-regulated kinase (ERK) was measured by Western blot analysis 1 week after cauterization.

Results: The area of corneal neovascularization was significantly reduced by 44% in the 30 mg·kg−1·day−1 group and by 66% in the 60 mg·kg−1·day−1 group, compared with the control group (P = 0.014 and P < 0.0001). Corneal VEGFR2 messenger RNA expression was higher in the control group than in the sorafenib-treated groups. The expression of phosphorylated ERK in rat corneas was suppressed in the sorafenib-treated groups but not in the control group.

Conclusions: Oral administration of a multikinase inhibitor (sorafenib) significantly reduced the development of experimental corneal neovascularization in a dose-dependent manner. This inhibitory effect is probably related to the suppression of ERK phosphorylation by sorafenib.

© 2012 Lippincott Williams & Wilkins, Inc.

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