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G.A. Limb, K. Matter, S.E. Moss, P.T. Khaw; Mmp-1 Associates with Mitochondria in Glial Müller Cells and Accumulates on Mitochondria and Perinuclear Region During Apoptosis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4549.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Müller glial cells are known to play an important role in the pathogenesis of retinal proliferative disease, but the mechanisms that control Müller cell proliferation resulting in reactive gliosis are not well understood. Our previous studies pointed to an intracellular accumulation of MMP-1 at various stages of the cell cycle, for which we have now investigated its precise localization within the cell. Methods: Müller cells in culture were examined by confocal microscopy using various monoclonal and polyclonal antibodies to MMP-1 and Golgi apparatus, as well as lysosomal and mitochondrial marker dyes. Cells were also transfected with an epitope tagged MMP-1 construct to confirm localization of this enzyme. In addition, cells were treated with staurosporine to examine the pattern of accumulation of MMP-1 during apoptosis. Results: The results showed that MMP-1 was colocalized with mitochondria and with nuclei in some cells, but not with the Golgi apparatus or lysosomes. Transfection of Müller cells with an HA-tagged MMP-1 construct confirmed mitochondrial localization, as did western blotting of mitochondrial lysates, which revealed the presence of this enzyme. Apoptotic cells exhibited a marked accumulation of MMP-1 associated with mitochondria, in addition to perinuclear staining of fragmented nuclei. Conclusions: These observations indicate that MMP-1 is strongly associated with mitochondria in Müller cells, and suggest that this matrix degrading enzyme may have an important intracellular role during apoptotic cell death. This may influence the survival and proliferation of Müller cells during retinal proliferative disease.
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