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Yang Hu, Ming-kai Lin, Kyungwon Lee, Ying Chen, Scott Mitchell, Jian-xing Ma; Therepeutic Effects Of An Anti-lrp6 Antibody On Laser-induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3915.
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Choroidal neovascularization (CNV) is a severe complication of age-related macular degeneration (AMD). Recent evidence has suggested that the Wnt signaling pathway mediates angiogenesis. The purpose of this study is to investigate the pathogenic role of Wnt signaling in CNV and explore the therapeutic potential of a novel Wnt signaling inhibitor on CNV.
Monoclonal antibody, anti-LRP6-mAb, was raised using the ligand-binding domain of LRP6. Its specificity and Wnt-blocking activity were confirmed. Adult Brown Norway rats and C57/BL6 mice were photocoagulated in the retina using a diode laser (Keeler, UK) to induce CNV. On the same day, laser induced CNV animals were intravitreally injected with a mouse anti-LRP6-mAb in both eyes, with non-specific mouse IgG as negative control. Total levels of LRP6, β-catenin and VEGF in the eyecup were determined by Western blot analysis one week after the injection. The neovascular area of lesions in laser induced CNV rats were quantified by FITC-dextran angiography in flat-mounted eyecup at two weeks after injection. The fundus angiograph with/without fluorescein was examined at three weeks post the injection.
Levels of total LRP6, β-catenin and VEGF were elevated in both laser-induced CNV rat and mouse eyecups at one week after photocoagulation, as compared to untreated animals, suggesting activation of the Wnt pathway. Significant reductions of LRP6, β-catenin and VEGF expression were observed in the eyes with a single intravitreal injection of anti-RP6-mAb, when compared to control group injected with mouse IgG. Moreover, anti-LRP6-mAb reduced the neovascular area of lesions after injection and decreased the grade 4 lesions at in laser induced CNV rats.
The Wnt signaling pathway is activated in laser-induced CNV animals and plays a pathogenic role in the CNV. Anti-LRP6-mAb has therapeutic effect in CNV.
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