Universität zu Köln

Zhang, Wei, Schonberg, Alfrun, Hamdorf, Matthias, Georgiev, Tihomir, Cursiefen, Claus and Bock, Felix . Preincubation of donor tissue with a VEGF cytokine trap promotes subsequent high-risk corneal transplant survival. Br. J. Ophthalmol.. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2079

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Abstract

Aims Pathological neovascularisation of the host bed and the transplant itself is the main risk factor for graft rejection after corneal transplantation. This study aims to prevent this process by preincubation of the corneal donor tissue ex vivo with an antivascular endothelial growth factor (VEGF) cytokine trap blocking additional postsurgical hemangiogenesis and lymphangiogenesis to promote high-risk graft survival. Methods The donor tissue was preincubated with a VEGFR1R2 cytokine trap for 24 hours prior to murine high-risk corneal transplantation (human IgG Fc was used as the control). The distribution of VEGFR1R2 Trap in the cornea was investigated by immunohistochemistry. Corneas were excised to quantify the blood vessels (BVs) and lymphatic vessels (LVs) and draining lymph nodes (dLNs) were harvested to analyse the phenotype of dendritic cells (DCs) and T cells at week 1, 2 and 8 post-transplantation. Graft survival was compared between preincubation with VEGFR1R2 Trap and human IgG Fc in high-risk recipients. Results VEGFR1R2 Trap was present in the graft for at least 2 weeks after surgery and additionally diffused into the corneal recipient. BVs, LVs and macrophages in the whole cornea were significantly decreased 1-week and 2-week post-transplantation (p<0.05). In dLNs the frequency of CD11c+DCs was significantly reduced, whereas CD200R+ regulatory DCs were significantly increased after keratoplasty (p<0.05). Furthermore, long-term high-risk graft survival was significantly improved (p<0.01). Conclusions Preincubation of corneal donor tissue with a VEGFR1R2 cytokine trap can significantly promote subsequent high-risk corneal transplant survival and thereby opens new treatment avenues for high-risk corneal transplantation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhang, Wei UNSPECIFIED UNSPECIFIED UNSPECIFIED Schonberg, Alfrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamdorf, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgiev, Tihomir UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-569532
DOI:	10.1136/bjophthalmol-2021-319745
Journal or Publication Title:	Br. J. Ophthalmol.
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2079
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; COSTIMULATORY PATHWAYS; GRAFT-SURVIVAL; EYE DROPS; LYMPHANGIOGENESIS; NEOVASCULARIZATION; PHARMACOKINETICS; HEMANGIOGENESIS; NEUTRALIZATION; ANGIOGENESIS Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56953