Purchase this article with an account.
Alice Banh, Paula A. Deschamps, Jack Gauldie, Paul A. Overbeek, Jacob G. Sivak, Judith A. West-Mays; Lens-Specific Expression of TGF-β Induces Anterior Subcapsular Cataract Formation in the Absence of Smad3. Invest. Ophthalmol. Vis. Sci. 2006;47(8):3450-3460. doi: 10.1167/iovs.05-1208.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. Smad3, a mediator of TGF-β signaling has been shown to be involved in the epithelial-to-mesenchymal transformation (EMT) of lens epithelial cells in a lens injury model. In this study, the role of Smad3 in anterior subcapsular cataract (ASC) formation was investigated in a transgenic TGF-β/Smad3 knockout mouse model.
methods. TGF-β1 transgenic mice (containing a human TGF-β1 cDNA construct expressed under the αA-crystallin promoter) were bred with mice on a Smad3-null background to generate mice with the following genotypes: TGF-β1/Smad3−/− (null), TGF-β1/Smad3+/−, TGF-β1/Smad3+/+, and nontransgenic/Smad3+/+. Lenses from mice of each genotype were dissected and prepared for histologic or optical analyses.
results. All transgenic TGF-β1 lenses demonstrated subcapsular plaque formation and EMT as indicated by the expression of α-smooth muscle actin. However, the sizes of the plaques were reduced in the TGF-β1/Smad3−/− lenses, as was the level of type IV collagen deposition when compared with TGF-β1/Smad3+/− and TGF-β1/Smad3+/+ lenses. An increased number of apoptotic figures was also observed in the plaques of the TGF-β1/Smad3−/− lenses compared with TGF-β1/Smad3+/+ littermates.
conclusions. Lens-specific expression of TGF-β1 induced ASC formation in the absence of the Smad3 signaling mediator, suggests that alternative TGF-β-signaling pathways participate in this ocular fibrotic model.
This PDF is available to Subscribers Only