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Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis

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Abstract

Background

Choroidal neovascularisation (CNV) as a feature of exudative age-related macular degeneration (AMD) is partially regulated by retinal pigment epithelium (RPE). In this study, the effect of combinatory anti-angiogenic treatment was evaluated using a novel in vitro assay of RPE-induced angiogenesis.

Methods

RPE isolated from surgically excised CNV-membranes (CNV-RPE) was used to stimulate sprouting of endothelial cell (EC) spheroids in a 3D collagen matrix. The anti-angiogenic effect of solitary anti-VEGF antibodies (bevacizumab) was compared to a combinatory treatment with anti-VEGF and anti-FGF2 antibodies.

Results

Anti-VEGF treatment inactivated all RPE-derived VEGF but was unable to fully inhibit EC sprouting induced by CNV-RPE. Combined anti-VEGF/anti-FGF treatment inactivated both growth factors and reduced EC sprouting significantly.

Conclusions

RPE from CNV patients expresses angiogenic growth factors that act in part independently of VEGF. Targeted combinatory therapy can be superior to solitary anti-VEGF therapy. One possible candidate for combinatory therapy is FGF2.

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Acknowledgments

The authors wish to thank Beatrix Flügel, Renate Buchen and Anne Mattes for excellent technical support. This work was supported by funding from the Forschungskommission Freiburg (AS).

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Authors and Affiliations

  1. Cell Biology Lab, University Eye Hospital Freiburg, Killianstrasse 5, 79106, Freiburg, Germany

    Andreas Stahl, Lilija Paschek, Gottfried Martin, Nicolas Feltgen, Lutz L. Hansen & Hansjürgen T. Agostini

  2. Department of Ophthalmology, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany

    Hansjürgen T. Agostini

Authors
  1. Andreas Stahl
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  2. Lilija Paschek
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  6. Hansjürgen T. Agostini
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Correspondence to Hansjürgen T. Agostini.

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None of the authors has financial relationships with companies or organisations mentioned in the study.

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Stahl, A., Paschek, L., Martin, G. et al. Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis. Graefes Arch Clin Exp Ophthalmol 247, 767–773 (2009). https://doi.org/10.1007/s00417-009-1058-x

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  • DOI: https://doi.org/10.1007/s00417-009-1058-x

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