Effect of sorafenib on experimental choroidal neovascularization in the rat.
OBJECTIVE
This study was designed to evaluate the effect of sorafenib administration on laser-induced experimental choroidal neovascularization (CNV) in rats.


METHODS
A total of 36 rats were divided into three groups. Sorafenib, an oral, multitargeted receptor tyrosine kinase inhibitor, was administered at a dose of 10 mg/kg per day (n = 12) or 30 mg/kg per day (n = 12) for 1 day before the laser induction of CNV. Rats continued to receive the drug for 14 days. Fluorescein angiograms were analysed for CNV dye leakage and the thickness of CNV was assessed by histology. The levels of vascular endothelial growth factor, platelet-derived growth factor, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 mRNA were measured by the use of real-time quantitative reverse-transcription polymerase chain reaction.


RESULTS
Sorafenib-treated rats had significantly less fluorescence leakage as compared with vehicle-treated rats (P < 0.05), The CNV thickness in sorafenib-treated rats was significantly reduced as compared with vehicle-treated rats in a dose-dependent manner (P = 0.00163 for 10 mg/kg and P < 0.00001 for 30 mg/kg). After sorafenib (30 mg/kg) administration, expression of the vascular endothelial growth factor and intercellular adhesion molecule-1 genes was significantly decreased (P < 0.05 and P = 0.00802).


CONCLUSIONS
These results suggest that sorafenib may be potentially beneficial for the treatment of CNV in human; further studies on this subject are warranted.
Park
Young-Hoon
YH
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Roh
Sang Y
SY
Lee
Young-Chun
YC
D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage*; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D003199:Computer Systems; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005451:Fluorescein Angiography; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007834:Lasers; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011832:Radiation Injuries / Q000150:complications; D051381:Rats; D011914:Rats, Inbred BN; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009536:Niacinamide; D000077157:Sorafenib