Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency

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...

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Autores principales:	Deniz Hos, Anne Bukowiecki, Jens Horstmann, Felix Bock, Franziska Bucher, Ludwig M. Heindl, Sebastian Siebelmann, Philipp Steven, Reza Dana, Sabine A. Eming, Claus Cursiefen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/053fbcf09c38419296950040ef200857
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spelling	oai:doaj.org-article:053fbcf09c38419296950040ef2008572021-12-02T12:32:58ZTransient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency10.1038/s41598-017-07806-42045-2322https://doaj.org/article/053fbcf09c38419296950040ef2008572017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07806-4https://doaj.org/toc/2045-2322Abstract 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.Deniz HosAnne BukowieckiJens HorstmannFelix BockFranziska BucherLudwig M. HeindlSebastian SiebelmannPhilipp StevenReza DanaSabine A. EmingClaus CursiefenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deniz Hos Anne Bukowiecki Jens Horstmann Felix Bock Franziska Bucher Ludwig M. Heindl Sebastian Siebelmann Philipp Steven Reza Dana Sabine A. Eming Claus Cursiefen Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
description	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.
format	article
author	Deniz Hos Anne Bukowiecki Jens Horstmann Felix Bock Franziska Bucher Ludwig M. Heindl Sebastian Siebelmann Philipp Steven Reza Dana Sabine A. Eming Claus Cursiefen
author_facet	Deniz Hos Anne Bukowiecki Jens Horstmann Felix Bock Franziska Bucher Ludwig M. Heindl Sebastian Siebelmann Philipp Steven Reza Dana Sabine A. Eming Claus Cursiefen
author_sort	Deniz Hos
title	Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
title_short	Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
title_full	Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
title_fullStr	Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
title_full_unstemmed	Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency
title_sort	transient ingrowth of lymphatic vessels into the physiologically avascular cornea regulates corneal edema and transparency
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/053fbcf09c38419296950040ef200857
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Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency

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