Article Text

other Versions

PDF
Inhibition of choroidal neovascularization in mice by systemic administration of the multikinase inhibitor, sorafenib
  1. Eun Jee Chung (eunjee95{at}hanmail.net),
  2. Sulina Yoo,
  3. Hyeong Joon Lim,
  4. Suk Ho Byeon,
  5. Joon H. Lee,
  6. Hyoung Jun Koh (hjkoh{at}yuhs.ac)
  1. NHIC Ilsan Hospital, Korea, Republic of
  2. YUMC, Korea, Republic of
  3. R&D Center, EyeGene Inc, Korea, Republic of
  4. YUMC, Korea, Republic of
  5. Konyang University, Korea, Republic of
  6. Yonsei University, Korea, Republic of

    Abstract

    Background: To investigate the effect of orally administered sorafenib (Nexavar®, Bay-43-9006, Bayer Schering Pharma, Germany), a multikinase inhibitor, in a mouse model of choroidal neovascularization (CNV).

    Methods: Sorafenib or vehicle was administered orally to female C57BL/6 mice at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the following day. After 14 days, mice were perfused with fluorescein-labeled dextran, and the area of CNV was measured on choroidal flat mounts by image analysis. In some groups of mice, treatments were started 7 days after the laser photocoagulation to determine the effect of the agent on established CNV. Expression of phosphorylated extracellular signal-regulated kinase (p-ERK) in choroidal tissues was measured by Western-blot analysis to demonstrate the kinase inhibitory effect of sorafenib in intracellular signaling pathways involved in CNV formation.

    Results: Sorafenib significantly reduced the extent of CNV in a dose-dependent manner. The area of CNV was reduced by 43% in the 30-mg/kg/day group and by 61% in the 60-mg/kg/day group compared with vehicle-treated controls (both P < 0.0001). Oral administration of sorafenib also caused significant regression of established CNV. The area of CNV was reduced by 59% in the 30-mg/kg/day group and by 66% in the 60-mg/kg/day group compared with both baseline and control measurements (P < 0.0001). The expression of p-ERK in choroidal tissues was increased within 1 day of laser photocoagulation and remained elevated for 2 weeks. The expression of p-ERK was suppressed by sorafenib.

    Conclusions: Sorafenib demonstrated anti-angiogenic properties in a mouse model of CNV and may be useful in the treatment of CNV.

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Linked Articles

    • At a glance
      Harminder S Dua Arun D Singh