Abstract

SA.23.09

In vitro comparison of VEGF-Antagonists: Bevacizumab, but not Ranibizumab, is accumulated in RPE cells

Alexa Klettner1, Marie-Luise Kruse2, Tim Meyer3, Daniela Wesch3, Dieter Kabelitz3, Johann Roider1
1Klinik für Augenheilkunde, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel, 2Molekulare Gastroenterologie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel, 3Immunologie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel

Objective
Vascular Endothelial Growth Factor (VEGF) antagonists are currently the therapy of choice for age-related macular degeneration. In this study, we compared the effects of FDA-approved Ranibizumab and off-label used Bevacizumab on RPE cells, investigating their respective uptake by RPE cells over time.
Methods
Primary porcine RPE cells were treated with Bevacizumab or Ranibizumab, respectively. Uptake of the respective VEGF-antagonists was assessed with confocal laser scanning microscopy and flow cytometry. Cell death was assessed with MTT assay and VEGF secretion was measured with ELISA.
Results
When clinical doses were applied for 1 h, Bevacizumab was taken up by RPE cells as assessed by confocal laser scanning microscopy and flow cytometry. After 24h of incubation and further assessed after 1d, 5d and 7d, Bevacizumab was detected in RPE cells where it accumulated over time. The presence of Bevacizumab within RPE cells after 7d was confirmed by flow cytometry. While some Ranibizumab was found in RPE cells after 1h of incubation when assessed with confocal laser microscopy but not by flow cytometry, no signal above control was detected after 1d, 5d or 7d. Neither substance induced significant cell death after 7 days and no inhibitory effect on VEGF secretion was observed after day 3 of culture.
Conclusions
Bevacizumab, but not Ranibizumab, accumulates in RPE cells over time, implying substantial differences between these two drugs.

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