Abstract
Purpose: :
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.
Methods: :
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).
Results: :
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.
Conclusions: :
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.
Keywords: transplantation • neovascularization • cornea: basic science