@article {314131,
	title = {Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival.},
	journal = {Graefes Arch Clin Exp Ophthalmol},
	volume = {252},
	number = {11},
	year = {2014},
	month = {2014 Nov},
	pages = {1755-62},
	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.},
	issn = {1435-702X},
	doi = {10.1007/s00417-014-2749-5},
	author = {Emami-Naeini, Parisa and Dohlman, Thomas H and Omoto, Masahiro and Hattori, Takaaki and Chen, Yihe and Lee, Hyun Soo and Chauhan, Sunil K and Dana, Reza}
}
