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D.J. Dwivedi, J. Robertson, M.E. Fini, J.A. West–Mays; Requirement for MMP–9 in TGFß–Induced Anterior Subcapsular Cataract Formation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4740.
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© ARVO (1962-2015); The Authors (2016-present)
Matrix Metalloproteinases (MMPs) have been shown to play a functional role in epithelial to mesenchymal transition (EMT) during TGFß–induced anterior subcapsular cataract (ASC) formation. A new model of ASC using adenoviral gene delivery (AdTGFß1) was employed in MMP–9 knock out (KO) mice to examine the requirement of MMP–9 expression in TGFß–induced cataract formation.
Wild–type and MMP–9 KO mice, on an FVB background, aged 6–8 weeks were injected with recombinantion–deficient adenovirus containing cDNA coding for active porcine TGFß1 (AdTGFß1) or control vector (AdGFP) containing green fluorescent protein, into the anterior chamber of the eye. The animals were sacrificed at 4 and 21 days post–injection. The eyes were dissected, fixed for histology and stained with Masson’s Trichrome or used for immunohistochemical localization of α smooth muscle actin (α–SMA).
In the wild–type mice (day 4 (n=7); day 21 (n=2)) post–injection, adenovirally delivered active TGFß1, resulted in the formation of distinct anterior subcapsular plaques that were immunoreactive to α–SMA demonstrative of EMT. Additionally, Masson’s trichrome stain revealed aberrant matrix deposition in the fibrotic plaques of the wild–type mice at day 21. In contrast to these findings, MMP9 KO mice at 4 days (n=5) and 21 days (n=6) post–injection did not exhibit plaques and the lens epithelial cells showed no reactivity to α–SMA. In addition, no aberrantly deposited matrix was observed in the MMP9 KO lenses. Note that the eyes injected with the control vector, AdGFP (day 21), did not show any of the cataractous changes.
The lack of ASC formation in the MMP–9 KO mice suggests that MMP–9 expression is required for mediating the alterations associated with TGFß–induced subcapsular cataract formation. This mode of gene delivery (AdTGFß1) will be used in further studies using heterozygous mice to determine whether one copy of the gene is sufficient for the TGFß–induced cataractous changes to occur. Future studies will be aimed at determining the specific requirement(s) and mechanism by which MMP–9 mediates EMT and ASC formation in the lens.
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