title: Control of patterns of corneal innervation by Pax6.
abstract: OBJECTIVE
  Corneal nerves play essential roles in maintaining the ocular surface through provision of neurotrophic support, but genetic control of corneal innervation is poorly understood. The possibility of a neurotrophic failure in ocular surface disease associated with heterozygosity at the Pax6 locus (aniridia-related keratopathy [ARK]) was investigated.
  
  
  METHODS
  Patterns of corneal innervation were studied during development and aging in mice with different Pax6 dosages and in chimeras. Immunohistochemistry and ELISA-based assays were used to determine the molecular basis of defects seen in Pax6 mutants, and wound healing assays were performed.
  
  
  RESULTS
  In adults, the Pax6(+/-) epithelium was less densely innervated than the wild-type epithelium, and radial projection of epithelial nerves was disrupted. Neurotrophic support of the corneal epithelium appeared normal. Directed nerve projection correlated with patterns of epithelial cell migration in adult wild-types, but innervation defects observed in Pax6(+/-) mice were not fully corrected in wound healing or chimeric models where directed epithelial migration was restored.
  
  
  CONCLUSIONS
  Pax6 dosage nonautonomously controls robust directed radial projection of corneal neurons, and the guidance cues for growth cone guidance are not solely dependent on directed epithelial migration. There is little evidence that ARK represents neurotrophic keratitis.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Leiper
authors.forename: Jingxing
authors.initials: J
authors.lastname: Ou
authors.forename: Petr
authors.initials: P
authors.lastname: Walczysko
authors.forename: Romana
authors.initials: R
authors.lastname: Kucerova
authors.forename: Derek N
authors.initials: DN
authors.lastname: Lavery
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.forename: J Martin
authors.initials: JM
authors.lastname: Collinson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002465:Cell Movement; D003315:Cornea / Q000254:growth & development / Q000294:innervation*; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000502:physiology; D005136:Eye Proteins / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018398:Homeodomain Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009412:Nerve Fibers; D009416:Nerve Regeneration / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014404:Tubulin; D013373:Substance P