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Parisa Emami-naeini, Takaaki Hattori, Nambi Nallasamy, Sunil K. Chauhan, Reza Dana; Soluble VEGFR- 3 Inhibits Lymph- angiogenesis and Prolongs Corneal Graft Survival. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1150.
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Emergence of new lymphatics and/or blood vessels in the cornea can disrupt corneal immune privilege, thus jeopardizing corneal transplant survival. Soluble VEGF receptor- 3 (sVEGFR-3) consists of the human VEGF receptor- 3 extracellular domains fused to the Fc-domain which can capture and thus block the activity of both VEGF-C and D. The purpose of this study was to examine the effect of systemic sVEGFR-3 on corneal transplant survival and alloimmunity.
The effect of intraperitoneal administration of sVEGFR-3 was assessed on murine corneal transplant rejection and neovascularization. We also assessed the effects of sVEGFR-3 on T cell function (production of IFN-g by T cells) and allosensitization (mixed lymphocyte reaction, MLR).
sVEGFR-3 decreased lymph-angiogenesis. Additionally, it prolonged corneal graft survival (87.5% vs. 50% over 8 weeks) associated with the suppression of allosensitization seen in the MLR co-cultures (p=0.004). Moreover, sVEGFR-3 led to a 67% suppression in the number of IFN-g producing CD4 T cells as compared to the untreated controls.
sVEGFR-3 can decrease Th1- dependent allosensitization and corneal lymph-angiogenesis, raising the possibility that sVEGFR-3 may offer a novel therapeutic approach in modulating corneal immune and inflammatory conditions.
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