Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

Authors

  • Seungbum Kang MD,

    1. Department of Ophthalmology and Visual Science, College of Medicine
    2. Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • Ki Cheol Park PhD,

    1. Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • Keum-Jin Yang PhD,

    1. Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • Hyun-Su Choi MS,

    1. Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • So-Hee Kim BS,

    1. Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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  • Young-Jung Roh MD

    Corresponding author
    1. Department of Ophthalmology and Visual Science, College of Medicine
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  • Competing/conflicts of interest: No stated conflict of interest.

  • Funding sources: This work was supported by Clinical Research Institute Grant funded by The Catholic University of Korea, Daejeon St. Mary's Hospital.

Dr Young-Jung Roh, Department of Ophthalmology and Visual Science, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 62, Yoido-dong, Youngdungpo-gu, Seoul 150-713, South Korea. Email: youngjungroh@hanmail.net

Abstract

Background:  This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization.

Methods:  Choroidal neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane using laser photocoagulation. Following laser injury, the mice were divided into three groups and administered either vehicle, 1 mg/kg or 5 mg/kg of cediranib daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of choroidal neovascularization lesions was measured by choroidal flat mounts using fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the choroidal neovascularization lesions.

Results:  Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of choroidal neovascularization. The groups treated with 1 and 5 mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization lesions, respectively, compared with the control group treated with vehicle alone (P = 0.012). The size of the fluorescently labelled choroidal neovascularization complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P = 0.035).

Conclusions:  Cediranib inhibited laser-induced choroidal neovascularization in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration.

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