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Tgfbeta receptor expression in lens: implications for differentiation and cataractogenesis.
R U de Iongh1, C Gordon-Thomson, C G Chamberlain
1Department of Anatomy and Histology and Institute for Biomedical Research (F13), The University of Sydney, Sydney, NSW 2006, Australia. robbdei@anatomy.usyd.edu.au
Experimental Eye Research
|June 1, 2001
Summary
Lens epithelial cells gain responsiveness to transforming growth factor beta (TGFbeta) with age due to increased TGFbeta receptor expression. Fibroblast growth factor-2 (FGF-2) enhances this responsiveness.
Area of Science:
- Ophthalmology and Vision Science
- Cell Biology
- Developmental Biology
Background:
- Transforming growth factor beta (TGFbeta) can induce cataract-like changes in the eye lens.
- Lens epithelial cell responsiveness to TGFbeta is age-dependent, with neonatal cells unresponsive, while weanling and adult cells respond.
- The underlying mechanisms for this age-related change in TGFbeta responsiveness are not fully understood.
Purpose of the Study:
- To investigate the expression patterns of TGFbeta receptors (TbetaRI and TbetaRII) during rat lens development.
- To determine the effect of fibroblast growth factor-2 (FGF-2) on TGFbeta responsiveness and TbetaR expression in lens epithelial cells.
Main Methods:
- Spatio-temporal expression of TbetaR was examined using immunofluorescence, immunoblotting, RT-PCR, and in situ hybridization.
- Lens explants were utilized to study the impact of FGF-2 on TGFbeta responsiveness and TbetaR expression.
- Western blotting identified multiple molecular weight forms of TbetaRI and TbetaRII.
Main Results:
- TbetaRI and TbetaRII expression increased in the lens epithelium from postnatal day 3 (P3) to P21.
- Lens explants from younger rats (P9) were unresponsive to TGFbeta, while older explants (P13) showed cataractous changes.
- FGF-2 treatment of P9 explants led to increased TbetaR expression and enhanced TGFbeta responsiveness.
Conclusions:
- Increased expression of TGFbeta receptors during postnatal lens development underlies the age-related change in TGFbeta responsiveness.
- Lens cells may express multiple forms of TGFbeta receptors.
- FGF-2 can modulate TbetaR expression and enhance lens cell sensitivity to TGFbeta, suggesting a role in FGF-induced responses and fiber differentiation.