July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Local VEGF-A blockade modulates the microenvironment of corneal transplantion side
Author Affiliations & Notes
  • Felix Bock
    Ophthalmology, University of Cologne, Cologne, Germany
    CMMC, Universtity of Cologne, Cologne, Germany
  • Ann-Charlott Schneider
    Ophthalmology, University of Cologne, Cologne, Germany
    CMMC, Universtity of Cologne, Cologne, Germany
  • Claus Cursiefen
    Ophthalmology, University of Cologne, Cologne, Germany
    CMMC, Universtity of Cologne, Cologne, Germany
  • Manuel Koch
    Center for Biochemistry, Universtity of Cologne, Germany
    Institute for Dental Research and Oral Musculoskeletal Biology, Universtity of Cologne, Germany
  • Raphael Reuten
    Biotech Research and Innovation Centre (BRIC), Universtity of Copenhagen, Denmark
  • Esther Mahabir
    Comparative Medicine, Center for Molecular Medicine, Universtity of Cologne, Germany
  • Gabriele Braun
    Ophthalmology, University of Cologne, Cologne, Germany
  • Malte Heykants
    Comparative Medicine, Center for Molecular Medicine, Universtity of Cologne, Germany
  • Footnotes
    Commercial Relationships   Felix Bock, None; Ann-Charlott Schneider, None; Claus Cursiefen, None; Manuel Koch, None; Raphael Reuten, None; Esther Mahabir, None; Gabriele Braun, None; Malte Heykants, None
  • Footnotes
    Support  DFG BO 4489/1-1/2 (German Research Foundation (DFG) FOR2240 “(Lymph)angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye”); Center for Molecular Medicine Cologne, University of Cologne
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 895. doi:
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    • Get Citation

      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)

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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.

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