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Lies De Groef, Djoere Gaublomme, Els Janssens, Eline Dekeyster, Lieve Moons; Expression of MMP-2, -3, -9 and -14 in the Healthy and Diseased Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4921.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple studies in glaucoma patients and animal models, have reported differential expression and activity of matrix metalloproteinases (MMPs). These data have led to the hypothesis that MMPs are involved in glaucoma. However, their in vivo functions remain poorly understood and several contradictorily results prevent a clear definition of their causative role. Here, we describe the expression of MMP-2, -3, -9 and -14 in the healthy and diseased adult mouse retina.
Expression of MMP-2, -3, -9 and -14 was examined via immunohistochemical stainings. Vimentin, GFAP, Brn3a and SMI-32 were used as specific markers to discriminate between Müller glia, astrocytes, retinal ganglion cell (RGC) soma and axons, respectively. RGC degeneration and concomitant glial activation were induced via intravitreal injection of the glutamate analogue NMDA (20mM, 2µl). Single RGCs undergoing apoptosis were detected via intravitreally injected Alexa-488 labeled Annexin V.
In the adult mouse retina, MMP-2 is expressed in the inner retina by the processes and endfeet of Müller glia, as shown by co-localization of MMP-2 and vimentin. Cytoplasmic MMP-3 expression is seen in the RGC layer and inner nuclear layer. A subset of these MMP-3+ cells is also immunoreactive for Brn3a, however not all Brn3a+ cells are MMP-3+, hence MMP-3 is expressed by a subset of RGCs, and presumably also by amacrine cells. MMP-9 shows a strong expression in the inner limiting membrane, a subset of cells in the RGC layer, and in both the inner and outer nuclear layer. MMP-14 is expressed by bundles of RGC axons in the nerve fiber layer, from where its expression is extending through the optic nerve via the optic chiasm to the primary visual targets in the brain.
MMP-2, -3, -9 and -14 are present in the adult mouse retina in both neuronal and glial cell types. Given these expression patterns, it is expected that MMP-2, -3, -9 and/or -14 might be involved in the processes underlying RGC death and glial reactivity in the retina.Therefore, we are currently investigating the expression of these MMPs in an in vivo NMDA excitotoxicity model. Preliminary data indeed show that MMP-2 is upregulated in the NMDA treated retina.
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