title: Improved corneal wound healing through modulation of gap junction communication using connexin43-specific antisense oligodeoxynucleotides.
abstract: OBJECTIVE
  Gap junctions play a major role in corneal wound healing. This study used reproducible models of corneal wound healing to evaluate the effect of a gap junction channel modulator, connexin43 (Cx43) antisense oligodeoxynucleotides (AsODN), on corneal healing dynamics.
  
  
  METHODS
  A mechanical scrape wound model was used to evaluate Cx43 AsODN penetration and initial wound reepithelialization 12 hours postsurgery. Thereafter, detailed analyses of corneal edema, inflammation, and healing were performed in an excimer laser surface ablation model. In vivo confocal microscopy determined clinical parameters (edema, haze) and cellular changes (stromal hypercellularity, reepithelialization), whereas histology and immunohistochemistry were used to quantify stromal edema, inflammation, and reepithelialization.
  
  
  RESULTS
  Cx43 AsODN penetrated through the hydrophilic stroma where the epithelium had been removed and accumulated in the basal epithelium close to the wound edge. Twelve hours after scrape wounding, Cx43 AsODN-treated eyes showed a significant reduction in wound area compared with the vehicle alone (1.59±0.37 and 2.29±0.58 mm2, respectively, P<0.01). After excimer laser ablation, stromal edema and inflammation were reduced, with endothelial structures being clearly visible, and reepithelialization rates were again increased in Cx43 AsODN-treated eyes. Histologic analysis confirmed reduced edema in the central wound site and at the periphery of treated corneas (P<0.05), whereas immunohistochemistry showed lower Cx43 levels (P<0.05), reduced myofibroblast activation, and improved epithelial basal lamina deposition in antisense-treated wounds (P<0.01).
  
  
  CONCLUSIONS
  Application of Cx43 AsODN to the cornea reduces stromal edema and inflammation, promoting faster wound closure and a more uniform repair of the epithelial basal lamina after laser ablation.
authors.affiliation: Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Christina N
authors.initials: CN
authors.lastname: Grupcheva
authors.forename: Wilda T
authors.initials: WT
authors.lastname: Laux
authors.forename: Ilva D
authors.initials: ID
authors.lastname: Rupenthal
authors.forename: Jennifer
authors.initials: J
authors.lastname: McGhee
authors.forename: Charles N J
authors.initials: CN
authors.lastname: McGhee
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000493:pharmacokinetics*; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D065306:Corneal Injuries; D004195:Disease Models, Animal; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018031:Connexin 43; D009838:Oligodeoxyribonucleotides