title: Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization.
abstract: The connexin 43 (Cx43) mimetic peptide Gap27 was designed to transiently block the function of this gap junction. This study was undertaken to investigate the effect of Gap27 on corneal healing, inflammation and neovascularization.
  
  
  
  The effect of Gap27 on wound healing, inflammation and vascularization was assessed in primary human corneal epithelial cells (HCEC) in vitro and whole human corneas ex vivo, and in an in vivo rat wound healing model.
  
  
  
  Gap27 enhanced the wound closure of HCEC in vitro and accelerated wound closure and stratification of epithelium in human corneas ex vivo, but did not suppress the corneal release of inflammatory mediators IL-6 or TNF-α in vivo. In human corneas ex vivo, F4/80 positive macrophages were observed around the wound site. In vivo, topical Gap27 treatment enhanced the speed and density of early granulocyte infiltration into rat corneas. After 7 days, the expressions of TNF-α and TGFβ1 were elevated and correlated with inflammatory cell accumulation in the tissue. Additionally, Gap27 did not suppress VEGF release in organotypic culture, nor did it suppress early or late VEGFA expression or neovascularization in vivo.
  
  
  
  Gap27 can be effective in promoting the healing of superficial epithelial wounds, but in deep stromal wounds it has the potential to promote inflammatory cell migration and accumulation in the tissue and does not suppress the subsequent neovascularization response. These results support the proposal that Gap27 acts as a healing agent in the transient, early stages of corneal epithelial wounding.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, AlMadinah AlMunawwarah, Saudi Arabia. hmbadawy@taibahu.edu.sa.|International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy. hmbadawy@taibahu.edu.sa.
authors.forename: Hossein Mostafa
authors.identifier: 0000-0001-8675-0838
authors.initials: HM
authors.lastname: Elbadawy
authors.affiliation: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Mirabelli
authors.affiliation: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Xeroudaki
authors.affiliation: International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.
authors.forename: Mohit
authors.identifier: 0000-0002-5186-068X
authors.initials: M
authors.lastname: Parekh
authors.affiliation: International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bertolin
authors.affiliation: International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Breda
authors.affiliation: Department of Ophthalmology, Perugia General Hospital, University of Perugia, Perugia, Italy.
authors.forename: Carlo
authors.identifier: 0000-0002-3812-9219
authors.initials: C
authors.lastname: Cagini
authors.affiliation: International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.
authors.forename: Diego
authors.identifier: 0000-0002-6038-3977
authors.initials: D
authors.lastname: Ponzin
authors.affiliation: Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden.
authors.forename: Neil
authors.initials: N
authors.lastname: Lagali
authors.affiliation: International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000037:antagonists & inhibitors*; D017630:Connexins / Q000494:pharmacology*; D065306:Corneal Injuries / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018031:Connexin 43; D017630:Connexins; C500216:GJA1 protein, human; C580592:Gja1 protein, rat; D009842:Oligopeptides; C455880:gap 27 peptide