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A. Namavari, B. Y. J. T. Yue, A. Djalilian; Inhibition of Notch Activity by Gamma Secretase Inhibitor Delays Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6296.
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Previous studies have implicated Notch signaling in the proliferation and differentiation of corneal epithelial cells. This study was performed to investigate the role of Notch activity in corneal epithelial wound healing.
Adult Cd1 mice underwent superficial keratectomy to create a 2mm corneal epithelial defect. One group received a subconjunctival injection of 50uM N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylgly cine t-butyl ester (DAPT group) in 0.1% DMSO in BSS, and the control group received the vehicle. The healing process was followed under slit lamp microscopy by fluorescein staining. On the third day eyes were enucleated and stained for ki67 to evaluate the proliferation rate.
The wound healing in the DAPT group was delayed significantly compared to the control group. Proliferation rate (ki67 immunostaining) in the limbus was significantly lower in the DATP group and the cornea was covered by a single epithelial cell layer as opposed to 3-4 layers in the control group. Ki67 was not detected in the center of the cornea in either of the groups.
The inhibition of Notch activity during corneal epithelial wound healing negatively affects cellular proliferation and the healing process.
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