Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 53, Issue 11, Pages 7097-7108Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.12-9989
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- Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Tokyo, Japan
- Ministry of Health, Labor and Welfare, Tokyo, Japan
- Grants-in-Aid for Scientific Research [23390403, 23791994, 23659814] Funding Source: KAKEN
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PURPOSE. We investigated the involvement of the RhoA/Rho kinase (ROCK) signal transduction pathway in dexamethasone (DEX)-induced changes in aqueous outflow. METHODS. Using trabecular meshwork (TM) and Schlemm's canal endothelial (SCE) cells, RhoA activation was evaluated with a pull-down assay and myosin light chain phosphorylation was evaluated by Western blot analysis. Outflow facility was measured in perfused porcine anterior segment organ cultures treated with DEX and/or Y-27632, a selective ROCK inhibitor. The barrier function of the cultured cells on a micropore filter was evaluated by measuring the transendothelial electrical resistance. Collagen, fibronectin, and integrin mRNA expression levels were evaluated by quantitative real-time RT-PCR. RESULTS. Relative RhoA activities increased following stimulation with 100 nM DEX in TM and SCE cells. Perfusion with DEX decreased outflow facility by 31.9 +/- 14.3% compared to controls at 24 hours, but not by 50 mu M Y-27632 in addition to DEX. The transendothelial electrical resistance of the SCE cell monolayer was increased by 48.6 +/- 6.4% and 5.3 +/- 5.0% following DEX treatments without and with 10 mu M Y-27632, respectively, compared to controls. In TM cells, the mRNA expressions of COL4A1 and fibronectin were increased significantly by DEX treatment, but combined treatment with Y-27632 and DEX significantly inhibited the increase in COL4A1and fibronectin expression. CONCLUSIONS. Activation of the Rho/ROCK pathway in SCE cells contributes to the mechanism of DEX-induced changes in aqueous outflow. (Invest Ophthalmol Vis Sci. 2012;53:7097-7108) DOI:10.1167/iovs.12-9989
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