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Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis

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Abstract

Background

The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions.

Methods

The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay.

Results

Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs.

Conclusions

Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.

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Support

IZKF Erlangen (A9); SFB 643 (“Graduiertenkolleg”); independent research by Pfizer (Berlin, Germany)

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Authors and Affiliations

  1. Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen–Nürnberg (FAU), 91054, Erlangen, Bavaria, Germany

    Melanie Lipp & Jasmine Onderka

  2. Department of Ophthalmology, University of Cologne, Kerpener Str. 62, 50924, Cologne, NRW, Germany

    Franziska Bucher, Deniz Hos, Claus Cursiefen & Felix Bock

  3. Vasan Eye Bank Vasan Eye Care Hospital Group, Chennai, India

    Anand Parthasarathy

Authors
  1. Melanie Lipp
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  2. Franziska Bucher
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  3. Anand Parthasarathy
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  4. Deniz Hos
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  5. Jasmine Onderka
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  6. Claus Cursiefen
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  7. Felix Bock
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Corresponding author

Correspondence to Felix Bock.

Additional information

Melanie Lipp and Franziska Bucher contributed equally, and should be regarded as co-first authors.

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Lipp, M., Bucher, F., Parthasarathy, A. et al. Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis. Graefes Arch Clin Exp Ophthalmol 252, 943–949 (2014). https://doi.org/10.1007/s00417-014-2626-2

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  • DOI: https://doi.org/10.1007/s00417-014-2626-2

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