April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Role Of MMP-2 In TGFβ-induced Epithelial-to-mesenchymal Transition
Author Affiliations & Notes
  • Anna Korol
    Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Jennifer V. Robertson
    Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Judith A. West-Mays
    Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships  Anna Korol, None; Jennifer V. Robertson, None; Judith A. West-Mays, None
  • Footnotes
    Support  NIH EY017146
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6700. doi:
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      Anna Korol, Jennifer V. Robertson, Judith A. West-Mays; Role Of MMP-2 In TGFβ-induced Epithelial-to-mesenchymal Transition. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6700.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Epithelial-to-mesenchymal transition (EMT) is a pathological process leading to the formation of anterior subcapsular cataract. Mediated by transforming growth factor beta (TGFβ), EMT involves the transformation of the monolayer of lens epithelial cells (LECs) into "spindle shaped" myofibroblasts, manifesting as plaques beneath the lens capsule. Our lab has previously demonstrated that TGFβ treatment, and subsequent EMT of rat lenses, triggered the secretion of matrix metalloproteinases (MMPs) -2 and -9. Co-treatment of this in vitro lens cataract model with TGFβ and a MMP2/9 inhibitor suppressed plaque formation that was otherwise visible on the lens when solely treated with TGFβ. Having identified MMP-2 and MMP-9 as participants in the formation of cataracts, the individual role of MMP-2 in TGFβ-induced EMT in in vivo mouse lens epithelial cells was investigated further.

Methods: : Using an adenoviral gene transfer method, TGFβ was overexpressed in the eyes of MMP-2 knockout (KO) mice. An adenovirus containing the transgene encoding active TGFβ (AdTGFβ) or an empty vector (AdDL) was injected into the anterior chamber of the eyes of the KO mice or their wild-type (WT) littermates. Twelve days following injection the eyes were removed, histologically processed and used for immunohistochemical detection of α-smooth muscle actin (αSMA) (a marker of EMT).

Results: : Hematoxylin and Eosin staining revealed that both MMP-2 KO and WT mice injected with AdTGFβ exhibited distinct plaques consisting of a focal multilayering of LECs directly beneath an intact lens capsule. In contrast, the empty vector, AdDL, injection did not lead to subcapsular plaque formation and showed a normal lens epithelial monolayer in both MMP-2 KO and WT mice, showing that transformation of LECs by AdTGFβ is specifically due to TGFβ stimulation. Immunohistochemical detection revealed the distinct expression of αSMA in the cells of the lenses exhibiting LEC plaques, whereas AdDL-injected lenses produced no detectable αSMA in the LEC monolayer.

Conclusions: : These studies indicate that, in the absence of MMP-2, EMT can be induced in mouse LECs in response to TGFβ treatment. Additional studies in our lab show that mice lacking functional MMP-9 in vivo exhibit significant protection from EMT following AdTGFβ delivery, and to a lesser degree a protective MMP-9 deletion was also observed in mice with lens specific overexpression of TGFβ. These results combined with the current study suggest that, in contrast to MMP-9, MMP-2 is not necessary for the EMT of in vivo LECs in anterior subcapsular cataract formation.

Keywords: EMT (epithelial mesenchymal transition) • cataract • adenovirus 

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