title: Matrix metalloproteinases in the mouse retina: a comparative study of expression patterns and MMP antibodies.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs), a family of Zn(2+)-dependent endoproteases, have been shown to act as fine regulators of both health and disease. Limited research revealed that they are essential to maintaining ocular physiology and inordinate MMP activities have been linked to several neurodegenerative disorders of the retina, including age-related macular degeneration, proliferative diabetic retinopathy and glaucomatous optic neuropathies (GONs). Nevertheless, a clear definition of their pathology-exacerbating and/or -resolving actions is lacking, especially in the context of GONs, as most studies thus far merely focused on expression profiling in human patients. Therefore, in an initial step towards an improved understanding of MMP functions in the retina, we studied the spatial expression pattern of MMP-2, -3, -9 and MT1-MMP in the healthy mouse retina.
  
  
  METHODS
  The spatial expression pattern of MMP-2, -3, -9 and MT1-MMP was studied in the healthy mouse retina via immunohistochemical stainings, and immunoreactivity profiles were compared to existing literature. Moreover, we considered sensitivity and specificity issues with commercially available MMP antibodies via Western blot.
  
  
  RESULTS
  Basal expression of MMP-2,-3, -9 and MT1-MMP was found in the retina of healthy, adult mice. MMP-2 expression was seen in Müller glia, predominantly in their end feet, which is in line with available literature. MMP-3 expression was described for the first time in the retina, and was observed in vesicle-like structures along the radial fibers of Müller glia. MMP-9 expression, about which still discords exists, was seen in microglia and in a sparse subset of (apoptosing) RGCs. MT1-MMP localization was for the first time studied in adult mice and was found in RGC axons and Müller glia, mimicking the MT1-MMP expression pattern seen in rabbits and neonatal mice. Moreover, one antibody was selected for each MMP, based on its staining pattern in Western blot.
  
  
  CONCLUSIONS
  The present MMP immunoreactivity profiles in the mouse retina and validation of MMP antibodies, can be instrumental to study MMP expression in mouse models of ocular pathologies and to compare these expression profiles to observations from clinical studies, which would be a first step in the disentanglement of the exact role MMPs in ocular/retinal diseases.
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology; KU Leuven, Naamsestraat 61, Box 2464, B-3000, Leuven, Belgium. lies.degroef@bio.kuleuven.be.
authors.forename: Lies
authors.initials: L
authors.lastname: De Groef
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology; KU Leuven, Naamsestraat 61, Box 2464, B-3000, Leuven, Belgium. lien.andries@bio.kuleuven.be.
authors.forename: Lien
authors.initials: L
authors.lastname: Andries
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology; KU Leuven, Naamsestraat 61, Box 2464, B-3000, Leuven, Belgium. kim.lemmens@bio.kuleuven.be.
authors.forename: Kim
authors.initials: K
authors.lastname: Lemmens
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology; KU Leuven, Naamsestraat 61, Box 2464, B-3000, Leuven, Belgium. inge.vanhove@bio.kuleuven.be.
authors.forename: Inge
authors.initials: I
authors.lastname: Van Hove
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology; KU Leuven, Naamsestraat 61, Box 2464, B-3000, Leuven, Belgium. lieve.moons@bio.kuleuven.be.
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007124:Immunoenzyme Techniques; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D012160:Retina / Q000201:enzymology*
chemical_list: C507096:Mmp14 protein, mouse; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D053511:Matrix Metalloproteinase 14