Elevated Expression of Matrix Metalloproteinase-9 and Inflammatory Cytokines in Keratoconus Patients Is Inhibited by Cyclosporine A
| Autor: | Anuprita Ghosh, Krina Mihir, Arkasubhra Ghosh, Abhijit Sinha-Roy, Reshma Shetty, Rayne R. Lim, Shyam S. Chaurasia, A. R. Reshma, Sriharsha Nagaraj, Murali Subramani, Roger W. Beuerman, Rohit Shetty, Debashish Das, Ashwini Ranganath, Rudy M.M.A. Nuijts |
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| Přispěvatelé: | MUMC+: *AB Refractie Chirurgie Oogheelkunde (9), MUMC+: MA UECM Oogartsen MUMC (9), Oogheelkunde, RS: MHeNs - R3 - Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Keratoconus medicine.medical_treatment keratoconus Inflammation Proinflammatory cytokine ectasia Cellular and Molecular Neuroscience Internal medicine Cornea cornea medicine Corneal epithelium business.industry MMP9 medicine.disease eye diseases Sensory Systems IL6 epithelial cells body regions Ophthalmology Endocrinology medicine.anatomical_structure Cytokine Tears Tumor necrosis factor alpha sense organs medicine.symptom business TNF alpha cyclosporine A |
| Zdroj: | Investigative Ophthalmology & Visual Science, 56(2), 738-750. Association for Research in Vision and Ophthalmology |
| ISSN: | 0146-0404 |
| Popis: | Purpose The present study was designed to understand the role of inflammatory cytokines secreted by corneal epithelial cells in keratoconus (KC) and the response to treatment with cyclosporine A (CyA). Methods The study involved 129 Indian KC patients clinically graded according to Amsler-Krumeich classification and 20 healthy, nonectatic subjects as controls. Tear levels of matrix metalloproteinase-9 (MMP9), interleukin-6 (IL6), and tumor necrosis factor-α (TNFα) were measured using ELISA kits. Gene expression was measured by qPCR in corneal epithelial cells obtained by debridement from subjects undergoing ocular surface surgeries. In addition, epithelial cells were stimulated with TNFα and treated with CyA to study its role on MMP9 expression. Finally, 20 KC patients (27 eyes) with inflammatory symptoms were treated with topical CyA application. Results We observed that MMP9, TNFα, and IL6 levels were strongly upregulated at the mRNA level in KC patient epithelia. Similarly, tears collected from KC patients exhibited high levels of MMP9 and IL6 protein. Cyclosporine A treatment significantly reduced the mRNA expression levels of IL6 and TNFα in both short- and long-term treatments; however, it reduced MMP9 levels only in long-term treatment in cultured corneal epithelial cells. Subsequent treatment of KC patients with CyA for approximately 6 months reduced tear MMP9 levels and led to local reduction in corneal curvatures as determined by corneal topography maps. Conclusions The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients. Cyclosporine A treatment reduced MMP9 and inflammatory cytokine levels in an in vitro inflammation model system. In KC patients, CyA treatment reduced MMP9 levels measured in tears with concomitant arrest of disease progression. Therefore, CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts. (ClinicalTrials.gov number, NCT01746823.). |
| Databáze: | OpenAIRE |
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