Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 55, Issue 1, Pages 216-225Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.13-12689
Keywords
Fuchs' endothelial corneal dystrophy; corneal endothelium; microRNA
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Funding
- National Institutes of Health [NIH EY019874, EY001765]
- Medical Illness Counseling Center
- Deutsche Forschungsgemeinschaft [DFG MA 5110/2-1]
- Research to Prevent Blindness (Wilmer Eye Institute)
- Richard Lindstrom/Eye Bank Association of America Research Grant
- J. Willard and Alice S. Marriott Foundation
- Fuchs' Dystrophy Research Grant (Wilmer Eye Institute)
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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.
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