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Asadolah Movahedan, Ali R. Djalilian, Robert M. Lavker, Beatrice Y. Yue; Notch Activation and Inhibition in Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2033.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the role of Notch signaling in corneal epithelium by examining the effect of exogenous activation and inhibition of Notch, using an in-vivo model of mouse corneal epithelial wound healing.
Thirty three, 6-month-old C57Bl/6 mice were selected and divided into three groups. The first group was pre-treated topically with Notch inhibitor (gamma-secretase inhibitor) for 4 hours; the second group received Notch ligand (recombinant Jagged-1) and the control group received phosphate buffer solution (PBS). Under anesthesia, a 2.0 mm area of the central cornea was demarcated and the epithelium was removed by gentle scraping, excluding the limbal area. The treatment continued in each group for three consecutive days post-ablation. Slit lamp pictures of the cornea at 0, 24, 48 and 72 hours post-ablation were obtained. After complete re-epithelialization, the newly formed epithelium was scraped and samples were collected for RT-PCR. Cryo-stat sections were examined by immunofluorescent staining for proliferation (ki-67) and differentiation (Keratin-12 and Pax-6) markers.
The mean surfaced area replaced by new epithelial layer in 24 hours post ablation was 93.6±6.2% in Jag-treated group (p=0.02), 79.3±14.1% in GSI-treated group and 77.8±18.1% for control group. Cytokeratin-12 expression was decreased by Notch inhibition and increased by its activation compared to control group. Proliferation marker, ki67, did not show any significant change in immunostaining.
Notch activation slightly accelerated the rate of epithelial wound healing in first 24 hours after superficial keratectomy. The early effects of Notch in corneal wound healing might be more due to its role in differentiation rather than proliferation.
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