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Felix Bock, Ann-Charlott Schneider, Claus Cursiefen, Manuel Koch, Raphael Reuten, Esther Mahabir, Gabriele Braun, Malte Heykants; Local VEGF-A blockade modulates the microenvironment of
corneal transplantion side. Invest. Ophthalmol. Vis. Sci. 2019;60(9):895.
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© ARVO (1962-2015); The Authors (2016-present)
The microenvironment plays an important role in several immunological processes.VEGF-A not only regulates angiogenesis, but is known as a modulator of the immunemicroenvironment. Modulating the site of transplantation might be beneficial forsubsequent transplant survival. In this study we therefore analyzed the effect of alocal blockade of VEGF-A on the immune system in the inflamed cornea as the graftreceiving tissue.
As an optimal model for local drug application we used the murinemodel of suture-induced neovascularization and subsequent high-risk cornealtransplantation. Mice were treated with VEGFR1/R2 trap prior to transplantation. Weanalyzed corneal gene expression, as well as protein levels in the cornea and serumon the day of transplantation, 2 and 8 weeks later.
Local VEGF depletion prior to transplantation increases the expression of proinflammatoryas well as immune regulatory cytokines only in the cornealmicroenvironment, but not in the in the serum. Furthermore, local VEGFR1/R2 traptreatment significantly inhibits the infiltration of CD11c+ dendritic cells into thecornea. Subsequent increased corneal transplantation success was accompanied bya local upregulation of Foxp3 gene expression.
This study demonstrates that locally restricted VEGF depletion increasestransplantation success by modulating the receiving corneal microenvironment andinducing tolerogenic mechanisms.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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