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Mario Matthaei, Jianfei Hu, Huan Meng, Eva-Maria Lackner, Charles G. Eberhart, Jiang Qian, Haiping Hao, Albert S. Jun; Endothelial Cell Whole Genome Expression Analysis in a Mouse Model of Early-Onset Fuchs' Endothelial Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(3):1931-1940. doi: 10.1167/iovs.12-10898.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the endothelial gene expression profile in a Col8a2 Q455K mutant knock-in mouse model of early-onset Fuchs' endothelial corneal dystrophy (FECD) and identify potential targets that can be correlated to human late-onset FECD.
Diseased or normal endothelial phenotypes were verified in 12-month-old homozygous Col8a2 Q455K/Q455K mutant and wild-type mice by clinical confocal microscopy. An endothelial whole genome expression profile was generated by microarray-based analysis. Result validation was performed by real-time PCR. Endothelial COX2 and JUN expression was further studied in human late-onset FECD compared to normal samples.
Microarray analysis demonstrated endothelial expression of 24,538 genes (162 up-regulated and 172 down-regulated targets) and identified affected gene ontology terms including Response to Stress, Protein Metabolic Process, Protein Folding, Regulation of Apoptosis, and Transporter Activity. Real-time PCR assessment confirmed increased Cox2 (P = 0.001) and Jun mRNA (P = 0.03) levels in Col8a2 Q455K/Q455K mutant compared to wild-type mice. In human FECD samples, real-time PCR demonstrated a statistically significant increase in COX2 mRNA (P < 0.0001) and JUN mRNA (P = 0.002) and tissue microarray analysis showed increased endothelial COX2 (P = 0.02) and JUN protein (P = 0.04).
The present study provides the first endothelial whole genome expression analysis in an animal model of FECD and represents a useful resource for future studies of the disease. In particular endothelial COX2 up-regulation warrants further investigation of its role in FECD.
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