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Brian Ceresa, Joanne Peterson; Pharmacological Analysis of Epidermal Growth Factor Receptor Ligands on Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2584. doi: https://doi.org/.
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An active epidermal growth factor receptor (EGFR) is both necessary and sufficient for promoting the homeostasis of the corneal epithelium. However, stimulation of the EGFR with epidermal growth factor (EGF) has not been an effective strategy for accelerating the repair of damaged corneal epithelium. Since synthetic EGFR ligands are not available, we have examined the role of endogenous EGFR ligands in promoting corneal epithelial cell growth and migration. These findings will aid in developing alternative strategies for stimulating EGFR activity that will further our understanding of the progression and reversal of diseases of the corneal epithelium, such as corneal erosions.
The endogenous EGFR ligands were tested for their ability to induced EGFR phosphorylation and promote in vitro corneal wound healing, cell migration, and proliferation using immortalized corneal epithelial cells (hTCEpi cells).
All EGFR ligands can enhance the phosphorylation of the EGFR. Despite comparable levels of receptor phosphorylation, the ligands produced quantitatively different in vitro wound healing. Pharmacologically, betacellulin is the most potent and efficacious mediator of in vitro corneal epithelial wound healing.
In the absence of synthetic EGFR ligands to restore or maintain corneal epithelial homeostasis, we have examined the ability of other ligands to execute this function. Regarding efficacy in promoting in vitro corneal epithelial wound healing, betacellulin > HB-EGF > EGF. These data indicate alternative ligands should be considered as mediators wound healing/homeostasis in vivo.
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