Universität zu Köln

Notara, Maria, Refaian, Nasrin, Braun, Gabriele, Steven, Philipp, Bock, Felix and Cursiefen, Claus (2016). Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu. Invest. Ophthalmol. Vis. Sci., 57 (3). S. 928 - 940. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. We analyzed the effects of short-term ultraviolet A (UVA) irradiation on the putative limbal stem cell phenotype, limbal fibroblasts, corneal inflammation, and corneal (lymph) angiogenic privilege. METHODS. Primary human limbal epithelial cells and fibroblasts were irradiated with 5.2 J/cm(2) of UVA. The limbal epithelial cell phenotype was assessed using P63a, cytokeratin 15, integrin b1 (marking stem and transient amplifying cells), and cytokeratin 3 (a differentiation marker) as well as by a colony-forming efficiency (CFE) assay. An epithelial-fibroblast coculture model was used to compare the ability of irradiated and nonirradiated fibroblasts to support the putative limbal stem cell phenotype. The effects of the conditioned media of irradiated and nonirradiated cells on proliferation and tube formation of human lymphatic and blood endothelial cells also were tested. The levels of factors related to angiogenesis and inflammation were assessed in a protein array and using ELISA. RESULTS. Ultraviolet A induced phenotypical changes of limbal epithelial cells, as their CFE and putative stem cell/transient amplifying marker expression decreased. Limbal epithelial cells cocultured with UVA-irradiated limbal fibroblasts also exhibited differentiation and CFE decrease. Conditioned media from irradiated limbal epithelial cells and fibroblasts inhibited lymphatic endothelial cell proliferation and tube network complexity. Levels of monocyte chemoattractant protein 1 (MCP1) were reduced following UVA irradiation of both cell populations, while levels of IFN-gamma increased in irradiated limbal epithelial cells. CONCLUSIONS. These data imply a key role of cellular components of the limbal niche following short-term UVA irradiation. Overall, UVA irradiation leads to dysfunction of these cells and a anti(lymph) angiogenic and anti-inflammatory micromilieu.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Notara, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Refaian, Nasrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Steven, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281994
DOI:	10.1167/iovs.15-18343
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	57
Number:	3
Page Range:	S. 928 - 940
Date:	2016
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; COLLAGEN CROSS-LINKING; EPITHELIAL STEM-CELLS; NITRIC-OXIDE SYNTHASE; CORNEAL HEMANGIOGENESIS; MACULAR DEGENERATION; LYMPHATIC VESSELS; SUNLIGHT EXPOSURE; UVA IRRADIATION; RISK-FACTOR Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28199