The connexin 43 mimetic peptide Gap27 is designed to transiently block the gap junction function. This study was undertaken to investigate the effect of Gap27 on corneal healing, inflammation and neovascularization.
Primary human corneal epithelial cells (HCEC) in vitro and whole human corneas ex vivo in addition to an in vivo rat wound healing model were used to assess the effect of Gap27 on wound healing, inflammation and vascularization.
Gap27 enhanced the wound closure of HCEC in vitro and accelerated wound closure and stratification of epithelium in human corneas ex vivo. Gap27 treatment 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 expression of TNF-α and TGF-β1 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 VEGF-A 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. The results support the proposition of Gap27 as a healing agent in the transient, early stages of corneal epithelial wounding.