Retinal MMP expression is upregulated in an excitotoxic mouse model of glaucoma

Purpose 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 disease onset and/or progression. However, their in vivo functions remain poorly understood and contradictorily results prevent a clear definition of their role. Here, we describe the expression of MMP‐2, ‐3, ‐9 and ‐14 in the retina of mice subjected to an acute excitotoxic glaucoma model. Methods Excitotoxic RGC death was induced via intravitreal injection of 20 mM NMDA. Expression of MMP‐2, ‐3, ‐9 and ‐14 was examined via immunohistochemistry, Western blot and quantitative RT‐PCR. Results MMP‐2 and ‐3 are expressed by glia, presumably Müller glia, in the healthy retina and are strongly upregulated at 24h after NMDA injection. MMP‐9 expression, which is not detectable in naive retinas, is observed in RGCs at 24h post NMDA injection, which confirms its suggested role in RGC apoptosis. In the naive retina, MMP‐14 is expressed by bundles of RGC axons in the nerve fiber layer, from where its expression is extending through the optic nerve to the primary visual areas in the brain. Within the first 48h after NMDA injection, MMP‐14 expression increases and is also seen in the inner nuclear layer and both plexiform layers. Conclusion Our results reveal a strong upregulation of MMP‐2, ‐3, ‐9 and ‐14 in the mouse retina after NMDA injection, suggesting that these proteinases might be involved in excitotoxic neurodegeneration and/or glial reactivity. Further analysis of their involvement, including studies in MMP knockout mice, is currently ongoing.