Universität zu Köln

Brash, James T., Denti, Laura ORCID: 0000-0002-6000-5765, Ruhrberg, Christiana and Bucher, Franziska (2019). VEGF188 promotes corneal reinnervation after injury. JCI Insight, 4 (21). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

Vascular endothelial growth factor A (VEGF) induces angiogenes is and vascular hyperpermeability in ocular tissues and is therefore a key therapeutic target for eye conditions in which these processes are dysregulated. In contrast, the therapeutic potential of VEGF's neurotrophic roles in the eye has remained unexploited. In particular, it is not known whether modulating levels of any of the 3 major alternatively spliced VEGF isoforms might provide a therapeutic approach to promote neural health in the eye without inducing vascular pathology. Here, we have used a variety of mouse models to demonstrate differences in overall VEGF levels and VEGF isoform ratios across tissues in the healthy eye. We further show that VEGF isoform expression was differentially regulated in retinal versus corneal disease models. Among the 3 major isoforms - termed VEGF120, VEGF164, and VEGF188 - VEGF188 was upregulated to the greatest extent in injured cornea, where it was both necessary and sufficient for corneal nerve regeneration. Moreover, topical VEGF188 application further promoted corneal nerve regeneration without inducing pathological neovascularization. VEGF isoform modulation should therefore be explored further for its potential in promoting neural health in the eye.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brash, James T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Denti, Laura UNSPECIFIED orcid.org/0000-0002-6000-5765 UNSPECIFIED Ruhrberg, Christiana UNSPECIFIED UNSPECIFIED UNSPECIFIED Bucher, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-129432
DOI:	10.1172/jci.insight.130979
Journal or Publication Title:	JCI Insight
Volume:	4
Number:	21
Date:	2019
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	2379-3708
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; OXYGEN-INDUCED RETINOPATHY; SOLUBLE VEGF; EYE DROPS; ANTI-VEGF; EXPRESSION; ISOFORMS; MOUSE; NEOVASCULARIZATION; ANGIOGENESIS Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12943