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Abstract
The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.
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1 St. Vincent’s Hospital, The Catholic University of Korea, Department of Ophthalmology and Visual Science, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
2 St. Vincent’s Hospital, The Catholic University of Korea, Department of Ophthalmology and Visual Science, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224); Duke University School of Medicine, Department of Ophthalmology, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
3 The Catholic University of Korea, Department of Microbiology, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
4 Duke University School of Medicine, Department of Ophthalmology, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961); Duke University School of Medicine, Department of Pharmacology and Cancer Biology, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)