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Different properties of VEGF-antagonists: Bevacizumab but not Ranibizumab accumulates in RPE cells

  • Retinal Disorders
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Abstract

Background

Vascular endothelial growth factor (VEGF) antagonists are currently the therapy of choice for age-related macular degeneration. Here 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 24 h 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 1 h 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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Acknowledgements

The authors would like to thank A. Pfaff, S. Luick, and M. Marquardt for their excellent technical assistance and Dr. H. Oberg for his helpful discussions.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Kiel, Campus Kiel, Hegewischstr. 2, 24105, Kiel, Germany

    Alexa Karina Klettner & Johann Roider

  2. Department of Molecular Gastroenterology, University of Kiel, Campus Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany

    Marie-Luise Kruse

  3. Department of Immunology, University of Kiel, Campus Kiel, Michaelisstr. 5, 24105, Kiel, Germany

    Tim Meyer, Daniela Wesch & Dieter Kabelitz

  4. Department of Ophthalmology, University of Kiel, Hegewischstr. 2, 24105, Kiel, Germany

    Alexa Karina Klettner

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  1. Alexa Karina Klettner
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  2. Marie-Luise Kruse
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  3. Tim Meyer
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  4. Daniela Wesch
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  5. Dieter Kabelitz
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Corresponding author

Correspondence to Alexa Karina Klettner.

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DOG Forschungsförderung

Financial disclosure

Ranibizumab for this research was supplied by Novartis

The authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data if requested.

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Klettner, A.K., Kruse, ML., Meyer, T. et al. Different properties of VEGF-antagonists: Bevacizumab but not Ranibizumab accumulates in RPE cells. Graefes Arch Clin Exp Ophthalmol 247, 1601–1608 (2009). https://doi.org/10.1007/s00417-009-1136-0

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  • DOI: https://doi.org/10.1007/s00417-009-1136-0

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