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B. A. Tucker, M. J. Young; Elevated Matrix Metalloproteinases Expression in the Retina of the Healer Mouse Creates a Permissive Environment for Retinal Regeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):44.
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© ARVO (1962-2015); The Authors (2016-present)
The MRL/Mpj (healer) mouse is an established model for autoimmune studies, and recently identified as having a profound ability to undergo scarless regeneration of the ear and heart. This regenerative capacity has been linked to elevated levels of MMP-2 and -9, giving this mouse the ability to degrade and remove basement membrane molecules. Although elevated MMP expression has been reported in a variety of somatic tissues, little is known about the level of expression and involvement of MMPs in the retina of this mouse. Therefore, the purpose of this study was to investigate whether there is increased MMP expression, and subsequently, decreased expression of basement membrane molecules in the MRL mouse retina.
All experiments were performed using MRL (healer), rd1 (retinal degeneration), and C57bl/6 (controls) retinas from 60-90 day old mice. Western blotting, immunocytochemistry, and in-situ and gel zymography were used to assess the level of expression and localization of both pro and active MMP-2 and -9. While western blot and immunocytochemical analyses were used to determine the level and location of basement membrane molecule expression. Immunocytochemistry and in situ zymography was analyzed using laser scanning confocal microscopy, whereas western blots and gel zymographs were digitized for densitometric analysis.
Compared to C57bl/6 (control), MRL mice exhibit elevated levels of MMP-2 and -9 throughout the retina. In correlation with elevated MMP expression, the MRL retina contains lower levels of the inhibitory extracellular matrix components CD44 and Neurocan, both of which are known to negatively influence axon extension and neuronal regeneration.
Elevated MMP expression observed in the MRL mouse retina decreases the levels of inhibitory basement membrane molecules, priming the retina for regeneration.
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