title: Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.
abstract: OBJECTIVE
  Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis.
  
  
  METHODS
  Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymography. Expression patterns of network candidates were revealed with immunohistochemistry, comparing physiological appearance and changes in a spontaneous recurrent uveitis model.
  
  
  RESULTS
  TIMP2 protein expression was found to be decreased in both the vitreous and the retina of a spontaneous model for autoimmune uveitis (equine recurrent uveitis [ERU]), and TIMP2 activity was significantly reduced in ERU vitreous. Functionally associated MMPs such as MMP2, MMP14, and MMP9 were found to show altered or shifted expression and activity. Although MMP2 decreased in ERU vitreous, MMP9 expression and activity were found to be increased. These changes were reflected by profound changes within uveitic target tissue, where TIMP2, MMP9, and MMP14 decreased in expression, whereas MMP2 displayed a shifted expression pattern. LCN2, a potential stabilizer of MMP9, was found prominently expressed in equine healthy retina and displayed notable changes in expression patterns accompanied by significant upregulation in autoimmune conditions. Invading cells expressed MMP9 and LCN2.
  
  
  CONCLUSIONS
  This study implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network, together with altered expression of functionally related MMPs.
authors.affiliation: Institute of Animal Physiology, Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Hofmaier
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.forename: Barbara
authors.initials: B
authors.lastname: Amann
authors.forename: Roxane L
authors.initials: RL
authors.lastname: Degroote
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Deeg
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000662:veterinary*; D015153:Blotting, Western; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D006734:Horse Diseases / Q000201:enzymology*; D006736:Horses; D054834:Lipocalins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012008:Recurrence; D012160:Retina / Q000201:enzymology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014605:Uveitis / Q000201:enzymology / Q000662:veterinary*; D014822:Vitreous Body / Q000201:enzymology
chemical_list: D054834:Lipocalins; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases