Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization

• DOI: 10.1111/bph.13568
• Publication Date: 2016-08-27T01:17:09Z
• Authors: Hossein Mostafa E...; Pierfrancesco Mir...; Maria Xeroudaki; Mohit Parekh; Marina Bertolin; Claudia Breda; Carlo Cagini; Diego Ponzin; Neil Lagali; Stefano Ferrari
• Keywords: Male; 0301 basic medicine; Wistar; Neovascularization, Physiologic; Epithelium; Connexins; Mice; 03 medical and health sciences; Animals; Humans; Rats, Wistar; Physiologic; Neovascularization; Pharmacology; Inflammation; Wound Healing; Animal; Epithelium, Corneal; Corneal; Research Papers; Rats; Ophthalmology; Disease Models, Animal; Connexin 43; Disease Models; Oftalmologi; Oligopeptides; Corneal Injuries

Background and PurposeThe 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.Experimental ApproachThe effect of Gap27 on wound healing, inflammation and vascularization was assessed in primary human corneal epithelial cells (HCEC)in vitroand whole human corneasex vivo, and in anin vivorat wound healing model.Key ResultsGap27 enhanced the wound closure of HCECin vitroand accelerated wound closure and stratification of epithelium in human corneasex vivo, but did not suppress the corneal release of inflammatory mediators IL‐6 or TNF‐αin vivo. In human corneasex 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 neovascularizationin vivo.Conclusions and ImplicationsGap27 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.