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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†,‡

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

Author Information

*Department of Ophthalmology, Sahmyook Medical Center, Seoul Adventist Hospital, Seoul, Korea

Department of Ophthalmology and Visual Science

Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Reprints: Choun-Ki Joo, Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul St Mary's Hospital, 505 Banpo-Dong, Seocho-Gu, Seoul 137-040, Korea (e-mail: ckjoo@catholic.ac.kr).

Supported by the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090136).

J. W. Seo and S. -H. Chung contributed equally to this study and should both be considered as first authors.

The authors state that they have no conflicts of interest to disclose.

Received January 27, 2011

Accepted July 20, 2011

© 2012 Lippincott Williams & Wilkins, Inc.