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Lithium stabilizes the polarized lens epithelial phenotype and inhibits proliferation, migration, and epithelial mesenchymal transition
Author(s) -
Stump RJW,
Lovicu FJ,
Ang SL,
Pandey SK,
McAvoy JW
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2049
Subject(s) - microbiology and biotechnology , epithelial–mesenchymal transition , vimentin , lens (geology) , tight junction , epithelium , cell polarity , chemistry , cell migration , myofibroblast , cell growth , actin , cell , downregulation and upregulation , biology , pathology , immunohistochemistry , immunology , biochemistry , medicine , paleontology , genetics , gene , fibrosis
Posterior capsule opacification (PCO) is a common complication of cataract surgery caused by epithelial mesenchymal transition (EMT) and aberrant lens cell growth. One path to prevention depends on maintaining the quiescent lens epithelial phenotype. Here we report that lithium chloride (LiCl) is a potent stabilizer of the lens epithelial phenotype. In lens epithelial explants (controls), at low cell density, cells readily depolarized, spread out, and proliferated. By contrast, in the presence of LiCl, cells did not spread out or exhibit migratory behaviour. Using concentrations of 1–30 m M LiCl we also showed that cell proliferation is inhibited in a dose‐dependent manner. Confocal microscopy and immunohistochemistry for ZO‐1 and E‐cadherin showed that LiCl treatment maintained tight junctions at the apical margins of cells. Taken together with measurements of cell heights, this showed that the cells in LiCl‐treated explants maintained the apical baso‐lateral polarity and cobblestone‐like packing that is characteristic of lens epithelial cells in vivo . Significantly, the effects of LiCl also extended to blocking the potent EMT/cataract‐promoting effects of transforming growth factor β (TGFβ) on lens epithelial cells. In TGFβ‐treated explants, cells progressively dissociated from one another, taking on various elongated spindle shapes and strongly expressing α‐smooth muscle actin (α‐SMA). These features are characteristic of PCO. In both rat and human capsulorhexis explants, LiCl treatment effectively blocked the accumulation of α‐SMA and maintained the cells in a polarized, adherent, cobblestone‐packed monolayer. These findings highlight the feasibility of applying molecular strategies to stabilize lens epithelial cells and prevent aberrant differentiation and growth that leads to cataract. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.