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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-11-2014 | Basic Science

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

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

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 11/2014

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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Title: Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival
Authors: Parisa Emami-Naeini
Thomas H. Dohlman
Masahiro Omoto
Takaaki Hattori
Yihe Chen
Hyun Soo Lee
Sunil K. Chauhan
Reza Dana
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 11/2014
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-014-2749-5

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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