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Yen-Chiao Wang, Yujin Zhang, Lingling Zhang, Yuka Okada, Chia-Yang Liu; Overexpression of TGF-a is detrimental to the corneal epithelial development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):963.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous study showed that conditional overexpression of TGFα in mouse keratocytes resulted in corneal epithelial hyperproliferation followed by subsequent degeneration. In this study, we examined the potential mechanism of the corneal degeneration caused by TGF-a.
KeraR/tet-O-TGFα bitransgenic (TG) mice were generated by naturally crossing KeraR driver mice which express rtta specifically in mouse stromal keratocytes with the effector mice tet-O-TGFα. TG mice were administered with doxycycline (Dox) for TGFα overexpression from embryonic day 12.5 (E12.5) to different developing stages including E14.5, E16.5, E18.5, postnatal day 0 (P0) and P7. Single transgenic littermates were used as controls (CTR). Mouse samples were subjected to Western blot, HE staining and transmission electron microscope (TEM) and immunofluorescence staining (IFS) to evaluate ocular surface conditions.
TGFα overexpression by the corneal stroma of TG mice after Dox induction was confirmed by Western blot. Although, the expressions of K12 keratin and Pax6 in the central corneal region remained intact, while gradually lost in corneal peripheral region. On the other hand, Keratin 13 expression was extended in corneal peripheral region. Furthermore, the hyperproliferative epithelial cells were not connected with desmosomes in the TG as compared with those in CTR at P7.
These data suggest that loss of desmosomes in cell-cell junction could be a critical reason to the corneal degeneration. Overexpression of TGF-alpha not only triggered an aberrative proliferation of corneal epithelial cells but lacking the formation of desmosomes to tight them together via intermediate filament. In addition, overexpression of TGF-a may deplete limbal epithelial stem cell phenotype and lead to conjunctivalization. Together, our data indicated that excess of TGF-a is detrimental to corneal epithelium development.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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