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A. K. Klettner, T. Meyer, F. Möhle, M.-L. Kruse, D. Wesch, D. Kabelitz, J. Roider; Uptake and Storage of Bevacizumab in RPE Cells Affect Its Physiological Function. Invest. Ophthalmol. Vis. Sci. 2010;51(13):465.
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The VEGF-antagonists Bevacizumab and Ranibizumab are widely used in anti-VEGF therapy to treat wet age-related macular degeneration. Both products have been developed from the same monoclonal murine anti-VEGF antibody and are often considered equally effective and interchangeable. In our studie, we investigate potential differences between these two agents with regard to their effects on retinal pigment epithelial cells (RPE).
In order to investigate the effect of Bevacizumab and Ranibizumab on the RPE, we used porcine primary RPE cells to analyse the uptake of either substance by flowcytometry and fluorescence microscopy, compared with the chimeric IGg1 antibody Rituximab. Additionally, we investigated the effect of the VEGF antagonists on cell proliferation by determining the cell number at day 0, day 3 and day 7 with a trypan blue exclusion assay, their effect on wound healing using a wound healing scratch assay and their effect on phagocytosis using photoreceptor outer segment (POS) opsonized FITC-labeled beads and fluorescence microscopy.
We found that Bevacizumab, but not Ranibizumab or Rituximab, is taken up and stored in RPE cells for at least 7 d (latest investigated time point). Both Bevacizumab and Ranibizumab slow down RPE cell proliferation, with a more profound effect of Bevacizumab compared to Ranibizumab. Neither substance impairs RPE wound healing ability. Most importantly, Bevacizumab, but not Ranibizumab or Rituximab, seem to impair the ability of the RPE to ingest POS-opsonized latex-beads, indicating a negative effect of Bevacizumab on the ability of RPE cells to phagocytose POS.
Bevacizumab and Ranibizumab are not identical in their effects on RPE cells. Bevacizumab is taken up and stored in RPE cells, which has a negative effect on the RPE cells ability to phagocytose photoreceptor outer segments.
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