title: Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the pax6+/- mouse model of aniridia-related keratopathy.
abstract: OBJECTIVE
  Congenital aniridia due to heterozygosity for Pax6 is associated with ocular surface disease, including keratopathy. This study investigated how defects in glycoconjugate component of the cell surface of Pax6+/- could cause the abnormal cellular migration phenotypes associated with the disease.
  
  
  METHODS
  Immunohistochemistry, lectin-based histochemistry, conventional staining techniques, and proteomic assays were performed on eyes and cultured corneal epithelial cells from wild-type and Pax6+/- littermates. Wild-type cells were manipulated in culture to replicate the glycoconjugate abnormalities found in Pax6 heterozygotes and determine the consequences for wound healing.
  
  
  RESULTS
  Multiple glycoconjugate defects were found in Pax6-mutant cells. Lectin cytochemistry of corneal epithelial cells suggested a partial failure of glycoprotein trafficking. Blocking cell surface carbohydrate moieties in wild-type corneal cells caused wound-healing delays similar to those seen in untreated Pax6+/- cells.
  
  
  CONCLUSIONS
  Alterations to the cell surface glycoconjugate signature of Pax6+/- corneal epithelia restrict the ability of cells to initiate migration in response to wounding. This underlies the observed wound-healing delay in cultured Pax6+/- epithelia.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Aberdeen, United Kingdom.
authors.forename: Romana
authors.initials: R
authors.lastname: Kucerova
authors.forename: Jingxing
authors.initials: J
authors.lastname: Ou
authors.forename: Diane
authors.initials: D
authors.lastname: Lawson
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Leiper
authors.forename: J Martin
authors.initials: JM
authors.lastname: Collinson
mesh_terms: D000818:Animals; D015783:Aniridia / Q000378:metabolism*; D001692:Biological Transport; D018929:Cell Culture Techniques; D003316:Corneal Diseases / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000378:metabolism*; D005136:Eye Proteins / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D006001:Glycoconjugates / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D037102:Lectins; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology*; D020543:Proteome / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D014945:Wound Healing
chemical_list: D005136:Eye Proteins; D006001:Glycoconjugates; D018398:Homeodomain Proteins; D037102:Lectins; D008562:Membrane Glycoproteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D020543:Proteome; D012097:Repressor Proteins