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Graefe's Archive for Clinical and Experimental Ophthalmology
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 1/2008

01.01.2008 | Cornea

Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation

verfasst von: Felix Bock, Jasmine Onderka, Tina Dietrich, Björn Bachmann, Bronislaw Pytowski, Claus Cursiefen

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 1/2008

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Abstract

Purpose

Inflammatory corneal hem- and lymphangiogenesis occurring both prior to as well as after penetrating keratoplasty significantly increase the risk for subsequent immune rejections. The purpose of this study was to analyze whether the blocking anti-VEGFR3 antibody mF4-31C1 is able to inhibit the outgrowth of pathologic new lymphatic vessels in a mouse model of suture-induced, inflammatory corneal neovascularisation, and whether this antibody specifically inhibits lymphangiogenesis without affecting hemangiogenesis.

Methods

Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice (6 weeks old) and left in place for 7 days to induce neovascularisation. The treatment group (n = 9) received the anti-VEGFR3 antibody mF4-31C1 intraperitoneally on the day of surgery and 3 days later (0.5 mg/mouse). Control mice received an equal amount of control IgG solution. For immunohistochemistry, corneal flat mounts were stained with LYVE-1 as a specific lymphatic vascular endothelial marker and with CD31 as panendothelial marker. Morphometry was performed with the image analysis software analySIS^B (Soft Imaging Systems GmbH, Münster, Germany). To improve the objectivity and precision of the morphometrical analysis, we established a modified method using grey filter sampling on monochromatic pictures.

Results

The mF4-31C1 antibody-treated mice displayed nearly complete inhibition of lymphangiogenesis compared with IgG controls (p < 0.006). In contrast, there was no significant inhibitory effect observed with respect to blood vessel growth (p > 0.05).

Conclusions

Inflammatory corneal lymphangiogenesis seems to depend on VEGFR3-signalling. By blocking this receptor the ingrowths of lymphatic vessels can be inhibited almost completely, and specifically without affecting hemangiogenesis. This may open new treatment options to promote (corneal) graft survival without affecting hemangiogenesis.
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Metadaten
Titel
Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation
verfasst von
Felix Bock
Jasmine Onderka
Tina Dietrich
Björn Bachmann
Bronislaw Pytowski
Claus Cursiefen
Publikationsdatum
01.01.2008
Verlag
Springer-Verlag
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 1/2008
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-007-0683-5

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