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

Elbadawy, HM; Mirabelli, P; Xeroudaki, M; Parekh, M; Bertolin, M; Breda, C; Cagini, C; ... Ferrari, S; + view all (2016) Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization. British Journal of Pharmacology , 173 (19) pp. 2880-2893. 10.1111/bph.13568. Green open access

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Abstract

BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: 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.

Type: Article
Title: Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bph.13568
Publisher version: https://doi.org/10.1111/bph.13568
Language: English
Additional information: © 2016 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: Animals, Connexin 43, Connexins, Corneal Injuries, Disease Models, Animal, Epithelium, Corneal, Humans, Inflammation, Male, Mice, Neovascularization, Physiologic, Rats, Rats, Wistar, Wound Healing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10055154
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