Local VEGF-A blockade modulates the microenvironment of the corneal graft bed.

Autor: Salabarria AC; Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany., Braun G; Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany., Heykants M; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Koch M; Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, University of Cologne, Cologne, Germany., Reuten R; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark., Mahabir E; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Cursiefen C; Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Bock F; Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2019 Sep; Vol. 19 (9), pp. 2446-2456. Date of Electronic Publication: 2019 Apr 03.
DOI: 10.1111/ajt.15331
Abstrakt: The microenvironment plays an important role in several immunological processes. Vascular endothelial growth factor-A (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 that a local blockade of VEGF-A in the inflamed cornea as the graft receiving tissue has on the immune system. We used the murine model of suture-induced neovascularization and subsequent high-risk corneal transplantation, which is an optimal model for local drug application. 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. Local VEGF depletion prior to transplantation increases the expression of pro-inflammatory as well as immune regulatory cytokines only in the corneal microenvironment, but not 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. This study demonstrates that locally restricted VEGF depletion increases transplantation success by modulating the receiving corneal microenvironment and inducing tolerogenic mechanisms.
(© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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