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Sanaz Gidfar, Asadolah Movahedan, Neda Afshar, Hossein Sagha, Ali R Djalilian; Progression of the Meibomian Gland Disease and Lid Margin Keratinization in Conditional Notch1 Knockout mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5494.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that conditional deletion of Notch1 in mouse corneal epithelium results in early barrier dysfunction. In this study we have looked into the serial changes that take place in the meibomian glands after Notch1 deletion to determine the primary and secondary changes.
Notch1 was conditionally deleted in 3 month old Notch1 flox/flox, K14-Cre-ERT +/- mice using intra-peritoneal injection of 1 mg/day 4-hydroxy-tamoxifen(4-OHT) for 5 days. Eyes were serially monitored after 4-OHT treatment by slit lamp examination and fluorescein staining. At different time points one subject of each group (N1-/- or WT) was sacrificed and the eyelid histology was examined by Hemptoxylin and Eosin and Periodic acid Schiff staining . Oil Red O staining was used to determine oil production by meibomian glands. To evaluate lid margin changes, per formed on frozen sections using anti-cytokeratin 10 and anti-cytoKeratin 8 antibodies.
The earliest change observed in the meibomian glands was loss of oil with preservation of the gross structure of the gland. Oil red O staining revealed loss of oil at 10-14 days after induction of Notch1 deletion. Two weeks after Notch1 deletiont there was no sign of lid margin keratinization compared to wild-type mice. Keratinization and cystic degeneration were both late findings seen after 4-6 weeks of 4-OHT induction as mentioned by other investigators.
Changes in the meibomian gland secretion occurrs early after induction of Notch1 knockout and seems to be a primary change whereas keratinization and cystic changes are thought to be secondary events. Notch1 appears to be important for differentiation of meibomian glands in particular the production of oily meibum. The complete loss of meibomian gland function over time is interesting given that Notch1 is only partially knocked out in our model. This suggests that secondary changes likely contribute to the complete degeneration of the gland.
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