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C.M. Garcia, J. Guo, G.P. Kwon, X. Wang, A. Chytil, H. Moses, D.C. Beebe; Signaling Through TGFßRII Is Not Required For Normal Lens Development Or For Myofibroblast Formation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2331.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The transdifferentiation of lens epithelial cells to myofibroblasts contributes to the formation of secondary cataracts. TGFß signaling has been implicated as the key regulator of this process. To test the role of TGFß signaling in lens myofibroblast formation we disrupted the gene for the type II TGFß receptor (TGFßRII) in the mouse lens. Methods: Mice expressing Cre recombinase driven by the Pax6 P0 promoter in the lens, corneal epithelium and pancreas were mated to mice that had critical exons of the TGFßRII gene flanked by loxP sequences. Progeny were genotyped using PCR and mice heterozygous for Cre and TGFßRII were mated to obtain wildtype, heterozygous and homozygous flox TGFßRII animals. RNA was isolated from the lenses of TGFßRIIflox/flox, Cre+ or Cre– mice for quantitative real–time PCR. Lens epithelial explants and isolated cells were cultured to induce the formation of myofibroblasts. Cells were prepared for histological examination and for immunostaining with antibodies against α–smooth muscle actin, phospho–Smad2 and Smad 4. Results: Lenses from TGFßRIIflox/flox Cre– and Cre+ animals were transparent and appeared normal in neonates and in adults. Cre+, TGFßRIIflox/flox mice expressed a maximum of 3% of the TGFßRII mRNA level found in wild type lenses. Lens epithelial explants from wild type and knockout animals showed similar levels and subcellular distributions of α–smooth muscle actin, phospho–Smad2 and Smad 4. Conclusions: Signaling through TGFßRII is not required for normal lens development or to activate α–smooth muscle actin expression from lens epithelial cells in vitro. Other pathways must be able to activate myofibroblast formation from lens epithelial cells.
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