Universität zu Köln

Matthaei, Mario, Zhu, Angela Y., Kallay, Laura, Eberhart, Charles G., Cursiefen, Claus and Jun, Albert S. (2014). Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy. Exp. Eye Res., 129. S. 13 - 18. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

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Abstract

Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p < 0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor 1D1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium. (C) 2014 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Matthaei, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Angela Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kallay, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Eberhart, Charles G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Jun, Albert S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-421383
DOI:	10.1016/j.exer.2014.10.011
Journal or Publication Title:	Exp. Eye Res.
Volume:	129
Page Range:	S. 13 - 18
Date:	2014
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1096-0007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROLIFERATIVE CAPACITY; MISSENSE MUTATIONS; OXIDATIVE STRESS; EXPRESSION; PROTEIN; COL8A2 Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42138