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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 11/2014

01.11.2014 | Basic Science

Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival

verfasst von: Parisa Emami-Naeini, Thomas H. Dohlman, Masahiro Omoto, Takaaki Hattori, Yihe Chen, Hyun Soo Lee, Sunil K. Chauhan, Reza Dana

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 11/2014

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Abstract

Purpose

To investigate the effect of VEGF-C and VEGF-D blockade via soluble VEGFR-3 (sVEGFR-3) on T cell allosensitization, corneal neovascularization, and transplant survival.

Methods

Corneal intrastromal suture placement and allogeneic transplantation were performed on BALB/c mice to evaluate the effect of sVEGFR-3 on corneal neovascularization. Soluble VEGFR-3 trap was injected intraperitoneally to block VEGF-C/D (every other day starting the day of surgery). Immunohistochemical staining of corneal whole mounts was performed using anti-CD31 (PECAM-1) and anti-LYVE-1 antibodies to quantify the levels of hem- and lymphangiogenesis, respectively. Mixed lymphocyte reaction (MLR) was performed to assess indirect and direct host T cell allosensitization and the frequencies of IFN-γ-producing T cells in the draining lymph nodes were assessed using flow cytometry. Graft opacity and survival was evaluated by slit-lamp biomicroscopy.

Results

Treatment with sVEGFR-3 resulted in a significant blockade of lymphangiogenesis 2 weeks post-transplantation and significantly prolonged corneal allograft survival compared to the control group at 8 weeks post-transplantation (87.5 % vs. 50 %), and this was associated with significant reduction in the frequencies of allosensitized T cells and decreased frequencies of IFN-γ–producing CD4 T cells.

Conclusions

Soluble VEGFR-3 suppresses corneal lymphangiogenesis and allograft rejection and may offer a viable therapeutic modality for corneal neovascularization and corneal transplantation.
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Metadaten
Titel
Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival
verfasst von
Parisa Emami-Naeini
Thomas H. Dohlman
Masahiro Omoto
Takaaki Hattori
Yihe Chen
Hyun Soo Lee
Sunil K. Chauhan
Reza Dana
Publikationsdatum
01.11.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 11/2014
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-014-2749-5

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