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Inhibition of choroidal neovascularisation in mice by systemic administration of the multikinase inhibitor, sorafenib
  1. E J Chung1,2,
  2. S Yoo2,
  3. H J Lim3,
  4. S H Byeon2,
  5. J H Lee4,
  6. H J Koh2
  1. 1
    Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyounggi-do, Korea
  2. 2
    The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea
  3. 3
    R & D Center, EyeGene Inc., Seoul, Korea
  4. 4
    Myunggok Eye Research Institute at Kim’s Eye Hospital, Konyang University College of Medicine, Nonsan, Korea
  1. Professor H J Koh, Department of Ophthalmology, Yonsei University College of Medicine, Sodaemungu Shinchondong 134, Seoul 120-752, Korea; hjkoh{at}yuhs.ac

Abstract

Background: To investigate the effect of orally administered sorafenib, a multikinase inhibitor, in a mouse model of choroidal neovascularisation (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-labelled 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 signalling 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 antiangiogenic properties in a mouse model of CNV and may be useful in the treatment of CNV.

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Footnotes

  • Competing interests: None.

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