Factor Vll-verteporfin for Targeted Photodynamic Therapy in a Rat Model of Choroidal Neovascularization
PURPOSE. To study the efficacy and safety of factor VII (fVII)-verteporfin for targeted photodynamic therapy (TPT) compared with nontargeted photodynamic therapy (PDT) in a rat model of choroidal neovascularization (CNV). fVII-verteporfin binds tightly and specifically to tissue factor, which is expressed on endothelial cells of COT but not normal vasculature.METHODS. Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, the rats were injected intravenously with fVII-verteporfin (0.5 and 1.0 mg/m2) or Visudyne (6.0 mg/ m2; QLT Inc., Vancouver, BC, Canada). Randomly selected lesions were treated with a 689-nm laser 30 or 60 minutes later. The lesions were evaluated by fluorescein angiography and histopathology.RESULTS. The rats treated with Visudyne PDT showed leakage in 75％ of the CNV lesions on day 7 and 100％ of lesions on day 14. Therats treated with fVII-verteporfin TPT at a dose of 0.5 mg/m2 showed leakage in 33％ and 36％ of the CNV lesions on days 7 and 14, respectively. When the dose was increased to 1. 0 mg/m2 for TPT, leakage was detected in 25％ and 23％ of the CNV lesions on days 7 and 14, respectively. No ocular side effect was detected by histopathologic evaluation.CONCLUSIONS. The frequency of leakage in CNV lesions was significantly reduced using fVII-verteporfin TPT compared with PDT. The efficacious dose with fVII-verteporfin was approximately 10％ of the dose usually used in nontargeted Visudyne PDT. Using fVII-verteporfin for TPT may improve the efficacy and safety of PDT for treating choroidal neovascularization.
Fang Lu Zhiwei Hu John Sinard Alan Garen Ron A Adelman
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06 Department of Obstetrics,Gynecology & Reproductive Sciences, Yale University School of Medicine, New Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06
国内会议
北京
英文
94-101
2012-05-11（万方平台首次上网日期，不代表论文的发表时间）