Universität zu Köln

Hos, Deniz, Bukowiecki, Anne, Horstmann, Jens, Bock, Felix, Bucher, Franziska, Heindl, Ludwig M., Siebelmann, Sebastian, Steven, Philipp, Dana, Reza, Eming, Sabine A. and Cursiefen, Claus (2017). Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema. Pharmacological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thickness due to delayed drainage of corneal edema and a trend towards prolonged corneal opacification. Notably, lymphatics are also detectable in the cornea of a patient with acute edema due to spontaneous Descemet's (basement) membrane rupture in keratoconus, mimicking this animal model and highlighting the clinical relevance of lymphangiogenesis in corneal fluid homeostasis. Together, our findings provide evidence that lymphangiogenesis plays an unexpectedly beneficial role in the regulation of corneal edema and transparency. This might open new treatment options in blinding diseases associated with corneal edema and transparency loss. Furthermore, we demonstrate for the first time that physiological lymphangiogenesis also occurs in primarily avascular sites.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hos, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Bukowiecki, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Horstmann, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Bucher, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindl, Ludwig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siebelmann, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Steven, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Dana, Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221962
DOI:	10.1038/s41598-017-07806-4
Journal or Publication Title:	Sci Rep
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC SKIN INFLAMMATION; GROWTH-FACTOR RECEPTOR-3; DRY EYE DISEASE; GRAFT-SURVIVAL; FACTOR-C; LYMPHANGIOGENESIS; TRANSPLANTATION; THROMBOSPONDIN-1; VASCULATURE; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22196