Assessment of Mouse VEGF Neutralization by Ranibizumab and Aflibercept

Abstract There are many articles using bevacizumab, ranibizumab, and aflibercept as effective anti-vascular endothelial growth factor (VEGF) drugs in mice. However, it has been reported that bevacizumab lacks the ability to neutralize mouse VEGF. Here, we assessed the interaction between ranibizumab or aflibercept and mouse VEGF, both in vitro and in vivo. In vitro, we analyzed the interaction of mouse VEGF-A with aflibercept or ranibizumab as the primary antibody by Western blot, and observed immunoreactive bands for mouse VEGF-A in the aflibercept-probed blot, but not in the ranibizumab-probed blot. In vivo, we assessed the effect of intravitreal injection of ranibizumab and aflibercept on oxygen induced retinopathy and the effect of multiple intraperitoneal injections of ranibizumab and aflibercept on neonatal mice, and found that anti-VEGF effects were observed with aflibercept, but not with ranibizumab in both experiments. Our results suggest that aflibercept but not ranibizumab interacts with mouse VEGF. When conducting experiments using anti-VEGF drugs in mice, aflibercept is suitable, but ranibizumab is not.