Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization
2016 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 173, no 19, 2880-2893 p.Article in journal (Refereed) Published
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 vitro and whole human corneas ex vivo, and in an in vivo rat wound healing model. Key ResultsGap27 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- 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 7days, the expressions of TNF- and TGF1 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. 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.
Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 173, no 19, 2880-2893 p.
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:liu:diva-132050DOI: 10.1111/bph.13568ISI: 000383668900006PubMedID: 27472295OAI: oai:DiVA.org:liu-132050DiVA: diva2:1038578
Funding Agencies|European Union - Regional, National and International Programs Initiative for the Mobility and Development of researchers careers (I-MOVE) ; European Cooperation in Science and Technology (EU-COST) program [BM1302, COST-STSM-BM1302-24766]2016-10-192016-10-172016-11-11