title: Integrin β1 is necessary for the maintenance of corneal structural integrity.
abstract: OBJECTIVE
  The precise role of a normal keratocyte in maintaining corneal structural integrity is unclear; it is generally considered to remain quiescent at the end of cell division. Given that integrins are essential for cell/extracellular matrix interactions, the authors tested the hypothesis that integrin expression by keratocytes is essential for corneal structure and function.
  
  
  METHODS
  Using a tamoxifen-dependent cre recombinase expressed under the control of a fibroblast-specific promoter/enhancer, the authors conditionally deleted the integrin β1 (Itgb1) gene in mouse keratocytes during the postnatal matrix maturation phase of the cornea. The effects of this deletion were monitored histologically and by macroscopic observation of the cornea.
  
  
  RESULTS
  The resultant cornea shows an initial thinning of the stroma, reduced space between collagen fibrils, loss of epithelial layers and subsequent edema, thickening of Descemet's membrane, and degenerative changes in the endothelial cell layer, with eventual scarring. These pathologic changes have some similarities to human corneal disease keratoconus. The phenotype did not develop when Itgb1 was deleted after complete corneal maturation.
  
  
  CONCLUSIONS
  Loss of integrin β1 expression in keratocytes during the phase of stromal maturation results in corneal thinning and edema. Keratocyte-ECM interaction is essential for matrix maturation and thus in the maintenance of corneal structural integrity. This model has relevance in understanding corneal diseases such as keratoconus.
authors.affiliation: Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Parapuram
authors.forename: Kun
authors.initials: K
authors.lastname: Huh
authors.forename: Shangxi
authors.initials: S
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015715:Corneal Edema / Q000378:metabolism / Q000473:pathology*; D003319:Corneal Stroma / Q000166:cytology* / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004728:Endothelium, Corneal / Q000473:pathology; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D019426:Integrases / Q000235:genetics; D019012:Integrin beta1 / Q000502:physiology*; D007640:Keratoconus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction
chemical_list: C530105:Ccnd1 protein, mouse; D019012:Integrin beta1; D019938:Cyclin D1; C045073:Cre recombinase; D019426:Integrases