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L.W. Reneker, L. Xie, A.C. Cully, P.A. Overbeek; TGFß1 Can Induce Changes in Cadherin and Crystallin Expression in Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3504.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: There is evidence that TGFß can induce pathological changes in lens epithelial cells. To analyze further the in vivo effects of TGFß on lens epithelial cells, we characterized transgenic mice that overexpress an activated form of TGFß1 in the eye. Methods: The transgenic mice express a modified human TGFß1 cDNA under the control of the lens–specific αA–crystallin promoter. Molecular changes in cell adhesion, cell cycle regulation, and fiber differentiation were assayed by in situ hybridization and immunohistochemistry. Results:As described previously, the transgenic mice exhibit ocular defects, including corneal opacity and cataracts. We characterized the lens phenotype in the most severely affected family (OVE920). We found that the epithelial cells in the TGFß1 transgenic lenses changed their morphology from cuboidal to columnar after embryonic day 18 (E18). E–cadherin was downregulated and N–cadherin upregulated in the lens epithelial cells of the homozygous TGFß1 transgenic mice. Cyclin D1, a G1–phase cyclin, was upregulated in the lens epithelium, but cell proliferation was not significantly altered. Additionally, more lens epithelial cells stained positive for activated (phosphorylated) Erk. Expression of fiber cell markers, including ß– and γ–crystallins, was detected in some areas of the lens epithelium where cells were elongated. Conclusion: Our results suggest that significantly elevated levels of TGFß1 in the eye can induce developmental change is the differentiation pathway for lens epithelial cells. These developmental changes precede the transdifferentiation to fibroblastic cells that can occur when older lens epithelial cells are exposed to activated TGFß.
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