title: Matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9, and TIMP-1, TIMP-2 and TIMP-3) and markers for vascularization in functioning and non-functioning bleb capsules of glaucoma drainage implants.
abstract: OBJECTIVE
  To investigate and compare functioning versus non-functioning glaucoma drainage implant (GDI) capsules for selective markers of extracellular matrix degradation and vascularity.
  
  
  METHODS
  In three samples of both functioning and non-functioning blebs, immunohistochemistry was used to determine the expression of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3 and CD31. A non-functioning bleb was defined as IOP >21 mmHg or <20% reduction in IOP from baseline with maximal tolerated medication. The samples were classified into five grades based on immunostaining: no staining, no significant staining, mild, moderate or marked staining.
  
  
  RESULTS
  Expression of MMP-1, MMP-2 and MMP-3 was mostly low in both functioning and non-functioning blebs. However, immunostaining of MMP-9 was marked in samples taken from functioning GDIs and correlated with the presence of vascular profiles in the luminal bleb. CD31 immunoreactivity was more intense in the outer layers of the bleb than in the inner layers. In non-functioning blebs, immunoreactivity for TIMP-3 was significant through the whole bleb wall, but only mild in the inner zone of functioning blebs. TIMP-1 and TIMP-2 were barely detectable.
  
  
  CONCLUSIONS
  Staining of TIMP-3 was seen to be lower in the vicinity of the small blood vessels. In avascular bleb wall, increased expression of TIMP-3 suggests its potential role in the inhibition of angiogenesis as reported previously in vivo. The abundance of MMP-9 in bleb capsule wall of relatively old patients might lead to weakened bleb capsule wall architecture and increasing filtration of aqueous humour through the capsule, which are reflected in a lower IOP.
authors.affiliation: Department of Ophthalmology, Päijät-Häme Central Hospital, Lahti, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Välimäki
authors.affiliation: Department of Ophthalmology, SILK, School of Medicine, University of Tampere, Tampere, Finland.|Tampere University Hospital, University of Tampere, Tampere, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Uusitalo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D003228:Conjunctiva / Q000098:blood supply*; D005260:Female; D005901:Glaucoma / Q000601:surgery; D020327:Glaucoma Drainage Implants; D006801:Humans; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1
keywords: angiogenesis; antiglaucoma medication; extracellular matrix; glaucoma tube surgery