Optometry Research Today is a free monthly online journal that collates and summarizes the latest research about Optometry, including details on myopia, optometric practice, therapy.

Lens-specific expression of TGF-beta induces anterior subcapsular cataract formation in the absence of Smad3.

Banh A, Deschamps PA, Gauldie J, Overbeek PA, Sivak JG, West-Mays JA

School of Optometry, University of Waterloo, Ontario, Canada.

PURPOSE: Smad3, a mediator of TGF-beta 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-beta/Smad3 knockout mouse model. METHODS: TGF-beta1 transgenic mice (containing a human TGF-beta1 cDNA construct expressed under the alphaA-crystallin promoter) were bred with mice on a Smad3-null background to generate mice with the following genotypes: TGF-beta1/Smad3(-/-) (null), TGF-beta1/Smad3(+/-), TGF-beta1/Smad3(+/+), and nontransgenic/Smad3(+/+). Lenses from mice of each genotype were dissected and prepared for histologic or optical analyses. RESULTS: All transgenic TGF-beta1 lenses demonstrated subcapsular plaque formation and EMT as indicated by the expression of alpha-smooth muscle actin. However, the sizes of the plaques were reduced in the TGF-beta1/Smad3(-/-) lenses, as was the level of type IV collagen deposition when compared with TGF-beta1/Smad3(+/-) and TGF-beta1/Smad3(+/+) lenses. An increased number of apoptotic figures was also observed in the plaques of the TGF-beta1/Smad3(-/-) lenses compared with TGF-beta1/Smad3(+/+) littermates. CONCLUSIONS: Lens-specific expression of TGF-beta1 induced ASC formation in the absence of the Smad3 signaling mediator, suggests that alternative TGF-beta-signaling pathways participate in this ocular fibrotic model.

Published 31 July 2006 in Invest Ophthalmol Vis Sci, 47(8): 3450-60.
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