Universität zu Köln

Matthaei, Mario, Hu, Jianfei, Kallay, Laura, Eberhart, Charles G., Cursiefen, Claus, Qian, Jiang, Lackner, Eva-Maria and Jun, Albert S. (2014). Endothelial Cell MicroRNA Expression in Human Late-Onset Fuchs' Dystrophy. Invest. Ophthalmol. Vis. Sci., 55 (1). S. 216 - 226. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. MicroRNAs (miRNAs) are a class of endogenous noncoding RNA and post transcriptionally modulate gene expression during development and disease. Our study investigated the differential miRNA expression in human Fuchs' endothelial corneal dystrophy (FECD) compared with normal endothelium to identify miRNA sequences that are involved in the pathogenesis of FECD. METHODS. Comparative miRNA expression profiles of endothelial samples obtained from FECD patients during lamellar corneal transplant surgery and from normal donor globes were generated using OpenArray plate technology. Differential expression of individual miRNAs was validated in the original and in independent samples using stem-loop RT qPCR assays. Expression of miRNA target genes was assessed using qPCR and tissue microarray (TMA) immunolabeling. RESULTS. Our results demonstrate downregulation of 87 miRNAs in FECD compared with normal endothelium (>3-fold change; P < 0.01). Correspondingly, DICER1, (encoding an endoribonuclease critical to miRNA biogenesis) showed a moderate but significant decrease in FECD samples (P < 0.05). Significant repression of three miR-29 family members (miR-29a-3p, miR-29b-2-5p, and miR-29c-5p) was paralleled by upregulation of their extracellular matrix associated mRNA targets collagen I and collagen IV. Tissue microarray immunolabeling showed histologically verifiable subendothelial collagen I and collagen IV deposition and increased endothelial laminin protein expression in FECD samples. CONCLUSIONS. The present study provides the first miRNA profile in FECD and normal endothelial cells and demonstrates widespread miRNA downregulation in FECD. Decreased endothelial expression of miR-29 family members may be associated with increased subendothelial extracellular matrix accumulation in FECD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Matthaei, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Jianfei UNSPECIFIED UNSPECIFIED UNSPECIFIED Kallay, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Eberhart, Charles G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Qian, Jiang UNSPECIFIED UNSPECIFIED UNSPECIFIED Lackner, Eva-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Jun, Albert S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-450752
DOI:	10.1167/iovs.13-12689
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	55
Number:	1
Page Range:	S. 216 - 226
Date:	2014
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 UNFOLDED PROTEIN RESPONSE; CORNEAL-DYSTROPHY; PENETRATING KERATOPLASTY; COLLAGEN EXPRESSION; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; OXIDATIVE STRESS; RENAL FIBROSIS; MOUSE MODEL; MIR-29 Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45075