Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Matthaei, M; Hu, J; Kallay, L; Eberhart, CG; Cursiefen, C; Qian, J; Lackner, EM; Jun, AS.
Endothelial cell microRNA expression in human late-onset Fuchs' dystrophy.
Invest Ophthalmol Vis Sci. 2014; 55(1):216-225
Doi: 10.1167/iovs.13-12689
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Lackner Eva-Maria
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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. 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. 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. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Cells, Cultured -
- Endothelium, Corneal - metabolism
- Fuchs' Endothelial Dystrophy - genetics
- Gene Expression Regulation -
- Humans -
- Immunohistochemistry -
- MicroRNAs - biosynthesis
- Microarray Analysis -
- Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
- Fuchs' endothelial corneal dystrophy
- corneal endothelium
- microRNA