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A. K. Klettner, J. B. Roider; Ranibizumab and Bevacizumab, But Not Pegaptanib, Show Similar Effiency in Neutralizing VEGF in vitro and May Act via Additional Pathways. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4574.
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VEGF antagonists are the therapy of choice for age-related macular degeneration. Ranibizumab ("Lucentis") and Pegaptanib ("Macugen") are FDA-approved, while Bevacizumab ("Avastin") is used off label. The aim of this study is to compare Lucentis, Avastin and Macugen directly in an in vitro system.
Porcine retina-RPE-choroid organ cultures were prepared from eyes obtain from the local abattoir and cultivated in a perfusion chamber. Tissues were treated with clinically relevant doses of Avastin (0,25 mg/ml), Lucentis (0,125 mg/ml) and Macugen (0,08 mg/ml), respectively. The supernatant was collected and the VEGF content was analysed with Elisa. Also, porcine primary RPE cell cultures were prepared, incubated with Lucentis and Avastin, respectively, and VEGF protein was analysed in Western Blot.
Bevacizumab and Ranibizumab, but not Pegaptanib, show a similar efficiency in neutralizing VEGF in this system. At clinical significant dose, both Bevacizumab (0,25 mg/ml) and Ranibizumab (0,125 mg/ml), neutralize VEGF completely for 6 hours, while Pegaptanib (0,08 mg/ml) showed no effect. Bevacizumab and Ranibizumab still show complete inhibition after 12 h, and inhibit VEGF significantly up to 16 h. Bevacizumab and Ranibizumab do not differ significantly. Moreover, both substances still neutralized VEGF completely for 6 h when diluted to 0,062 mg/ml (Avastin) and 0,031 mg/ml (Lucentis), respectively. After incubation with Bevacizumab or Ranibizumab, VEGF expression in RPE cells is significantly diminished, indicating additional pathways of VEGF inhibition.
Avastin and Lucentis show similar efficiency even when highly diluted, while Macugen does not show any effect in this system, which might offer an explanation for clinical experiences. Additionally, Avastin and Lucentis may show an impact on RPE cells on a cellular level.
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