Universität zu Köln

Salabarria, Ann-Charlott ORCID: 0000-0001-6829-2001, Braun, Gabriele, Heykants, Malte, Koch, Manuel, Reuten, Raphael ORCID: 0000-0002-9434-4108, Mahabir, Esther, Cursiefen, Claus and Bock, Felix (2019). Local VEGF-A blockade modulates the microenvironment of the corneal graft bed. Am. J. Transplant., 19 (9). S. 2446 - 2457. HOBOKEN: WILEY. ISSN 1600-6143

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Salabarria, Ann-Charlott UNSPECIFIED orcid.org/0000-0001-6829-2001 UNSPECIFIED Braun, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Heykants, Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Reuten, Raphael UNSPECIFIED orcid.org/0000-0002-9434-4108 UNSPECIFIED Mahabir, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-143239
DOI:	10.1111/ajt.15331
Journal or Publication Title:	Am. J. Transplant.
Volume:	19
Number:	9
Page Range:	S. 2446 - 2457
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-6143
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; REGULATORY T-CELLS; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; BLOOD-VESSELS; NEOVASCULARIZATION; LYMPHANGIOGENESIS; TRANSPLANTATION; SURVIVAL; HEMANGIOGENESIS Multiple languages Surgery; Transplantation Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14323