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|Title: ||The Role of MMPs, Smad3 and Heat Shock Proteins in TGF-β-Induced Anterior Subcapsular Cataract Development|
|Authors: ||Banh, Alice|
|Keywords: ||anterior subcapsular cataract formation|
transforming growth factor beta
rat lens culture
lens epithelial cells
heat shock proteins
|Approved Date: ||18-Jun-2007 |
|Date Submitted: ||2007 |
|Abstract: ||Transforming growth factor beta (TGF-β) has been implicated in anterior subcapsular cataract (ASC) development. In the first section of this thesis, an in-vitro rat lens model was used to determine the role of matrix metalloproteinases during TGF-β-induced ASC. In the second part, an in-vivo TGF-β transgenic and Smad3 knockout model was used to examine the role of Smad3 signaling pathway in TGF-β-induced ASC development. Lastly, an in-vitro rat lens epithelial explant culture model was used to investigate the potential role of heat shock proteins (Hsps) in TGF-β-induced epithelial-mesenchymal transition (EMT). Optical, morphological and molecular changes were analyzed in theses studies.
Results from cultured rat lenses show a significant increase of back vertex distance variability (decrease of sharpness and focus) during ASC development. Inhibition of MMPs eliminated the TGF-β-induced plaque formation. Similarly, the overexpression of TGF-β1 in transgenic mouse lenses leads to ASC formation and a decrease in lens optical quality in comparison to wild-type lenses, while TGF-β1/Smad3-/- (null) lenses show diminished TGF-β-induced effects. The plaques formed in the TGF-β1/Smad3-/- lenses are substantially smaller than in the TGF-β1/Smad3+/+ lenses. The morphological and molecular changes of TGF-β2/FGF-2 treated rat lens epithelial explants are similar to those found in the TGF-β2 treated rat lenses and transgenic TGF-β1 mouse lenses. Heat shock treatment prior to TGF-β treatment significantly reduced the effects of EMT in rat LECs.
In conclusion, MMP inhibition prevented TGF-β-induced ASC formation whereas heat shock treatment and the absence of Smad3 protein expression only reduced the severity of TGF-β-induced effects.|
|Program: ||Vision Science and Biology|
|Department: ||School of Optometry|
|Degree: ||Doctor of Philosophy|
|Appears in Collections:||Electronic Theses and Dissertations (UW)|
Faculty of Science Theses and Dissertations
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