Endothelial cell whole genome expression analysis in a mouse model of early-onset Fuchs' endothelial corneal dystrophy

Invest Ophthalmol Vis Sci. 2013 Mar 15;54(3):1931-40. doi: 10.1167/iovs.12-10898.


Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / genetics*
  • Disease Models, Animal
  • Endothelium, Corneal / metabolism*
  • Endothelium, Corneal / pathology
  • Female
  • Fuchs' Endothelial Dystrophy / genetics*
  • Fuchs' Endothelial Dystrophy / metabolism
  • Fuchs' Endothelial Dystrophy / pathology
  • Genes, jun / genetics*
  • Genome / genetics*
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Phenotype
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation*


  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human