Matrix Metalloproteinase 9 and Transglutaminase 2 Expression at the Ocular Surface in Patients with Different Forms of Dry Eye Disease

• Published in: Ophthalmology (Rochester, Minn.) Vol. 122; no. 1; pp. 62 - 71
• Main Authors: Aragona, Pasquale, MD, PhD, Aguennouz, M'Hammed, PhD, Rania, Laura, MD, PhD, Postorino, Elisa, MD, PhD, Sommario, Margherita Serena, MD, Roszkowska, Anna Maria, MD, PhD, De Pasquale, Maria Grazia, PhD, Pisani, Antonina, MD, Puzzolo, Domenico, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2015
• Subjects: Adult; Aged; Biomarkers - metabolism; Case-Control Studies; Caspase 3 - genetics; Caspase 3 - metabolism; Conjunctiva - enzymology; Eyelid Diseases - drug therapy; Eyelid Diseases - enzymology; Female; Glucocorticoids - therapeutic use; GTP-Binding Proteins; Humans; Immunohistochemistry; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Meibomian Glands - enzymology; Middle Aged; Ophthalmology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Single-Blind Method; Sjogren's Syndrome - drug therapy; Sjogren's Syndrome - enzymology; Surveys and Questionnaires; Tears - chemistry; Transglutaminases - genetics; Transglutaminases - metabolism; Bcl-2; SS; interferon-γ; Meibomian gland dysfunction; real-time polymerase chain reaction; TBUT; transglutaminase 2; MGD; MMP9; Sjögren syndrome; IL-6; interleukin-6; INF-γ; matrix metalloproteinase 9; tear film break-up time; RT PCR; B-cell lymphoma 2; TG2
• ISSN: 0161-6420; 1549-4713
• DOI: 10.1016/j.ophtha.2014.07.048

Objective To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. Design Case control study. Participants 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. Main Outcome Measures 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.