April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
MMP-3 EXPRESSION IN THE DAMAGED MOUSE RETINA: A ROLE IN GLIAL REACTIVITY?
Author Affiliations & Notes
  • Manuel Salinas-Navarro
    Laboratory for Neural Circuit Development and Regeneration, KU Leuven, Leuven, Belgium
  • Lies De Groef
    Laboratory for Neural Circuit Development and Regeneration, KU Leuven, Leuven, Belgium
  • Eline Dekeyster
    Laboratory for Neural Circuit Development and Regeneration, KU Leuven, Leuven, Belgium
  • Ingeborg Stalmans
    Department of Ophthalmology, KU leuven, Leuven, Belgium
  • Inge Van Hove
    Laboratory for Neural Circuit Development and Regeneration, KU Leuven, Leuven, Belgium
  • Lieve K M Moons
    Laboratory for Neural Circuit Development and Regeneration, KU Leuven, Leuven, Belgium
  • Footnotes
    Commercial Relationships Manuel Salinas-Navarro, None; Lies De Groef, None; Eline Dekeyster, None; Ingeborg Stalmans, None; Inge Van Hove, None; Lieve Moons, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4472. doi:
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      Manuel Salinas-Navarro, Lies De Groef, Eline Dekeyster, Ingeborg Stalmans, Inge Van Hove, Lieve K M Moons, ; MMP-3 EXPRESSION IN THE DAMAGED MOUSE RETINA: A ROLE IN GLIAL REACTIVITY?. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4472.

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

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Abstract

Purpose: Matrix metalloproteinase-3 (MMP-3) has been associated with neuro-inflammatory and neurodegenerative diseases. A recent transcriptome profiling study also revealed highly upregulated levels of MMP-3 mRNA in retinas after optic nerve axotomy. As the involvement of MMP-3 to optic neuropathies has been understudied, we investigated its role in RGC survival and glial reactivity in mice subjected to optic nerve crush (ONC), a model to study glaucoma pathophysiology

Methods: The left optic nerve was intraorbitally crushed in MMP-3 deficient (MMP-3-/-) and wild type (WT) mice and retinas were dissected at several survival intervals after crush (6, 12, 24 & 48h, 4 & 7d). Expression of MMP-3 was examined via immunohistochemistry (IHC) and western blot (WB). RGC survival was assessed at 4 and 7 days after ONC by quantifying the number of surviving RGCs after Brn3a immunostaining on whole mount retinas using distribution maps and automatical analyses. IHC for Iba-1, GFAP and GS was performed on retinal whole mounts and/or radial sections, which were all examined and photographed using confocal microscopy. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) is currently being analyzed via WB and IHC

Results: IHC revealed MMP-3 expression in the processes of Müller glia throughout the entire retina of the healthy mouse eye. MMP-3 protein expression dramatically increases at early time points after ONC, peaks at 4d after injury and is highly associated with glial cells, as confirmed by both WB and IHC. Strikingly, the number of surviving RGCs was found to be similar in MMP-3-/- and WT mice, both at 4 days (70 ± 9% vs 72 ± 6%; n=15) and at 7 days (22 ± 6% vs 25 ± 4%; n=10) post-surgery. IHC stainings for the glial cell markers Iba-1, GFAP and GS revealed a similar expression in both genotypes. To further investigate the underlying mechanisms we are currently analysing the spatio-temporal expression pattern of the endogenous MMP-3 inhibitor TIMP-1, in the retina of MMP-3-/- and WT mice subjected to ONC

Conclusions: MMP-3 expression, found in Muller glia cells in the healthy retina, is highly upregulated in the injured retina. Given its glial expression, MMP-3 could contribute to glial reactivity, implying an involvement in retinal homeostasis. However, MMP-3 deficiency did not protect retinas from ONC-induced RGC death. Future experiments aim at unraveling the role of this proteinase in glaucoma pathogenesis

Keywords: 519 extracellular matrix • 688 retina • 699 retinal glia  
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