title: Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease.
abstract: OBJECTIVE
  To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye.
  
  
  METHODS
  Case control study.
  
  
  METHODS
  Seventy-five female subjects divided into 3 groups: group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD).
  
  
  METHODS
  A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate.
  
  
  METHODS
  Conjunctival expression of MMP9 and TG2.
  
  
  RESULTS
  MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS.
  
  
  CONCLUSIONS
  The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.
authors.affiliation: Department of Experimental Medical-Surgical Specialties, Regional Referral Center for Ocular Surface Diseases, University of Messina, Messina, Italy. Electronic address: paragona@unime.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Aragona
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: M'Hammed
authors.initials: M
authors.lastname: Aguennouz
authors.affiliation: Department of Experimental Medical-Surgical Specialties, Regional Referral Center for Ocular Surface Diseases, University of Messina, Messina, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rania
authors.affiliation: Department of Experimental Medical-Surgical Specialties, Regional Referral Center for Ocular Surface Diseases, University of Messina, Messina, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Postorino
authors.affiliation: Department of Experimental Medical-Surgical Specialties, Regional Referral Center for Ocular Surface Diseases, University of Messina, Messina, Italy.
authors.forename: Margherita Serena
authors.initials: MS
authors.lastname: Sommario
authors.affiliation: Department of Experimental Medical-Surgical Specialties, Regional Referral Center for Ocular Surface Diseases, University of Messina, Messina, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Roszkowska
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: De Pasquale
authors.affiliation: Department of Biomedical Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Pisani
authors.affiliation: Department of Biomedical Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Puzzolo
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D003228:Conjunctiva / Q000201:enzymology*; D005141:Eyelid Diseases / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D019204:GTP-Binding Proteins; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008537:Meibomian Glands / Q000201:enzymology*; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016037:Single-Blind Method; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000201:enzymology*; D011795:Surveys and Questionnaires; D013666:Tears / Q000737:chemistry; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; C508600:IL6 protein, human; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D007371:Interferon-gamma; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D053148:Caspase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D019204:GTP-Binding Proteins