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Asadolah Movahedan, Ali R. Djalilian, Mercede Majdi, Hossein M. Sagha, Behrad Y. Milani, Robert M. Lavker, Beatrice Y. Yue; Notch Inhibition Accelerates Mouse Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3538.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the role of Notch signaling in corneal epithelial wound healing by examining the effect of exogenous inhibition of Notch1, in an in-vivo model of mouse corneal epithelial wound healing using excimer laser for superficial keratectomy.
Fourteen, 6-month-old C57Bl/6 mice were selected and divided into two groups. Under anesthesia, a 2 mm area of central corneal epithelium was removed by superficial keratectomy using excimer NIDEK EC-5000. The first group was treated topically with a gamma secretase inhibitor (GSI) and control group received the vehicle. Slit lamp pictures of cornea at 0, 24, 48 and 72 hours post-ablation were obtained. After complete re-epithelialization, the newly formed epithelium was harvested for RT-PCR. Cryostat sections were examined by immuno-fluorescent staining for proliferation (ki-67) and differentiation markers (Cytokeratin12).
The mean surface area replaced by the new epithelium at 24 hours post-ablation was 88.1 % ± 12.2 in GSI treated group (p=0.025) versus 69.7 ± 14.1% in control group. Notch inhibition was confirmed by reduced transcription of Hes-1 (a Notch downstream effector) by RT-PCR. Cytokeratin-12 expression was decreased by Notch inhibition through Gamma secretase inhibitor treatment in comparison with control group at 72 hours post-ablation. ki-67 expression didn’t show any significant difference between GSI and control groups.
Notch manipulation appears to affect the rate of wound healing in a murine model. Our in-vivo outcomes indicate a statistically significant increase in the rate of epithelial wound closure with pharmacologic inhibition of Notch signaling.
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