Universität zu Köln

Notara, Maria, Refaian, N., Braun, G., Steven, P., Bock, F. and Cursiefen, C. (2015). Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines. Stem Cell Res., 15 (3). S. 643 - 655. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1876-7753

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Abstract

Ultraviolet light B (UVB)-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiation are unclear. Here the effect of UVB irradiation on the putative stem cell phenotype, limbal niche cells and the subsequent effects on corneal (lymph)angiogenic privilege were investigated. Primary human limbal epithelial stem cells and fibroblasts were irradiated with 0.02 J/cm(2) of UVB, a low dose corresponding to 3 min of solar irradiation. UVB irradiation caused significant reduction of limbal epithelial and limbal fibroblast proliferation for 24 h, but apoptosis of limbal epithelial stem cells only. Moreover, UVB induced stem-like character loss of limbal epithelial cells, as their colony forming efficiency and putative stem cell marker expression significantly decreased. Interestingly, limbal epithelial cells co-cultured with UVB-irradiated limbal fibroblasts also exhibited loss of stem cell character and decrease of colony forming efficiency. Conditioned media from limbal epithelial cells inhibited lymphatic endothelial cell proliferation and tube network complexity; however this effect diminished following UVB irradiation. In contrast, pro-inflammatory and macrophage-recruiting cytokines such as TNF alpha, IFN gamma and MCP1 were significantly upregulated following cell irradiation of limbal fibroblasts. These data demonstrate the key role of the limbal stem cell niche in response to UVB and subsequent (lymph)angiogenic and inflammatory events. These data suggest that the known pro(lymph)angiogenic effect of UVB irradiation in pterygium is not linked to a direct up-regulation of pro-angiogenic cytokines, but rather to indirect macrophage-recruiting cytokines being upregulated after UVB irradiation. (C) 2015 The Authors. Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Notara, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Refaian, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steven, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-387428
DOI:	10.1016/j.scr.2015.10.008
Journal or Publication Title:	Stem Cell Res.
Volume:	15
Number:	3
Page Range:	S. 643 - 655
Date:	2015
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1876-7753
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; FACTOR BINDING PROTEIN-3; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; EPITHELIAL-CELLS; CORNEAL EPITHELIUM; FACTOR-BETA; MACULAR DEGENERATION; LYMPHATIC VESSELS; SUNLIGHT EXPOSURE Multiple languages Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38742