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K. Miki, M. Matsuoka, D. Muramatsu, A. Miki, K. Yokoi, C. Seidel, S. F. Hackett, P. A. Campochiaro; Comparison of Ranibizumab and Bevacizumab in Animal Models of Subretinal Neovascularization (NV). Invest. Ophthalmol. Vis. Sci. 2009;50(13):783.
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Ranibizumab (RBZ) and Bevacizumab (BCZ) do not cross-react with murine vascular endothelial growth factor (VEGF) making investigations in some mouse models impossible; therefore, we utilized transgenic mice that express human VEGF to investigate their effects.
The effects of intraocular injection of various concentrations of RBZ or BCZ were evaluated in transgenic mice with constitutive expression of VEGF in photoreceptors (rho/VEGF mice) or double transgenics with doxycycline-inducible expression of VEGF in photoreceptors (Tet/opsin/VEGF mice).
At P14, rho/VEGF transgenics had intraocular injection of 1 or 10 µg of RBZ or 1, 10, or 25 µg of BCZ. At P21, there was significant reduction in mean area of NV per retina in all eyes injected with RBZ or BCZ compared to injection of vehicle. At P28, eyes injected 10 µg, but not 1 µg of RBZ had less NV than eyes injected with vehicle, while eyes injected with 1, 10, or 25 ug of BCZ had a significantly less NV than eyes injected with vehicle or 1 ug of RBZ. Five days after injection of 25 µg of BCZ or 10 µg of RBZ (proportional to current clinical doses) in Tet/opsin/VEGF mice treated with 2 mg/ml of doxycycline in drinking water, the total retinal detachment (RD): partial RD: no RD ratio was 34.8%:26.1%:39.1% for BCZ compared to 90%:0%:10% for RBZ.
Both BCZ and RBZ strongly inhibited subretinal NV in rho/VEGF transgenics, but at equivalent doses the duration of effect was greater for BCZ. In the more aggressive Tet/opsin/VEGF model, at doses proportional to those used clinically, BCZ was significantly better than RBZ in prevention of retinal detachment.
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