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R. Stump, F. Lovicu, S. Ang, J. McAvoy; Lithium Chloride Maintains Lens Epithelial Polarity in vitro: Identification of Biochemical Targets. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4231.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that treatment with lithium chloride (LiCl), even in the presence of TGFß, can inhibit epithelial mesenchymal transition and maintain lens epithelial cells in a quiescent, polarized state in explant cultures. In order to identify potential biochemical targets for molecular approaches to controlling the aberrant growth and differentiation that occurs in posterior capsule opacification, we set out to identify the signaling pathways modulated by LiCl treatment.
Epithelial cells from postnatal day 21-30 rat lenses were explanted on their native capsule substratum. Immunohistochemistry and Western blotting were used to determine the influence of LiCl on the expression of key signaling molecules that are known to influence the behaviour of lens cells. Control explants were cultured in equivalent concentrations of NaCl.
LiCl-treated explants showed no evidence, unlike NaCl controls, of Wnt pathway activation as indicated by active ß-catenin translocation to the nucleus or phosphorylation of GSK3ß (Ser9). Importantly, LiCl-treated explants, unlike controls, maintained expression of the receptor tyrosine kinase inhibitor, Sprouty2, which is strongly expressed in the lens epithelium in vivo. Consistent with this, phospho-tyrosine, phospho-ERK and phospho-Src were significantly reduced in the cytoplasm of LiCl-treated lens epithelial cells compared with NaCl-treated controls. LiCl-treated explants, unlike controls, also maintained atypical PKC, a key component of the complex that generates cell polarity, at apical junctional complexes of lens epithelial cells.
This study indicates that, rather than activating Wnt/ß-catenin signaling as has been reported in many cellular systems, in polarized lens epithelial cells LiCl-treatment appears to have the opposite effect and inhibits this pathway. LiCl maintains Sprouty2 in the lens epithelial explants and this may have a role in inhibiting ERK and Src activation. Blocking these pathways appears to be important for maintenance of the lens cells in a polarised quiescent state.
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