Purchase this article with an account.
Hiroto Terasaki, Naoya Yoshihara, Makoto Shirasawa, Hiroki Otsuka, Shozo Sonoda, Taiji Sakamoto; Permeability of ranibizumab and bevacizumab through the polarized RPE cells in vitro. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3442.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate the penetration of ranibizumab and bevacizumab through the polarized RPE cells in vitro and its mechanism.
Highly polarized RPE cells were cultured in Boyden chamber (Sonoda S, et al. Nat Protoc, 2009). Polarization was confirmed by asymmetrical secretion of VEGF between apical and basal side and significant expression of ZO-1. Ranibizumab (1-100 μg/ml) or bevacizumab (2.5-250 μg/ml) were added to the upper chamber. After 3 hours, the medium in lower chamber was evaluated by measuring the concentration of them using ELISA. The effect of pharmacological inhibitors was evaluated to investigate the mechanism of permeation of ranibizumab/bevacizumab.
Ranibizumab was more permeable than bevacizumab through RPE layer at any concentration (2.0-2.6 times greater than bevacizumab, Mann-Whitney U, P<0.05). Light and electron microscopy showed no cytotoxic changes in either ranibizumab- or bevacizumab-treated RPE cells. Permeation of ranibizumab/bevacizumab was significantly inhibited by protein kinase C inhibitor in contrast to control.
Ranibizumab was more permeable than bevacizumab through highly polarized RPE cells. And its permeation through RPE cells was, at least in part, PKC-dependent. Considering its similarity to RPE in vivo, ranibizumab might be more effective than bevacizumab on the treatment for type 1 choroidal neovascularization.
This PDF is available to Subscribers Only