Local VEGF-A blockade modulates the microenvironment of corneal transplantion side

Abstract

Purpose : The microenvironment plays an important role in several immunological processes.
VEGF-A not only regulates angiogenesis, but is known as a modulator of the immune
microenvironment. Modulating the site of transplantation might be beneficial for
subsequent transplant survival. In this study we therefore analyzed the effect of a
local blockade of VEGF-A on the immune system in the inflamed cornea as the graft
receiving tissue.

Methods : As an optimal model for local drug application we used the murine
model of suture-induced neovascularization and subsequent high-risk corneal
transplantation. Mice were treated with VEGFR1/R2 trap prior to transplantation. We
analyzed corneal gene expression, as well as protein levels in the cornea and serum
on the day of transplantation, 2 and 8 weeks later.

Results : Local VEGF depletion prior to transplantation increases the expression of proinflammatory
as well as immune regulatory cytokines only in the corneal
microenvironment, but not in the in the serum. Furthermore, local VEGFR1/R2 trap
treatment significantly inhibits the infiltration of CD11c+ dendritic cells into the
cornea. Subsequent increased corneal transplantation success was accompanied by
a local upregulation of Foxp3 gene expression.

Conclusions : This study demonstrates that locally restricted VEGF depletion increases
transplantation success by modulating the receiving corneal microenvironment and
inducing tolerogenic mechanisms.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.