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Hideki Mochizuki, Junko Hirata, Yoshiaki Kiuchi; Effects of Rho Kinase Inhibitor on mRNAs Associated with Glaucoma Progression in Human Trabecular Meshwork Cells Following Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4473.
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Oxidative stress occurs in glaucoma and is known to increase two pro-inflammatory cytokines, IL-6 and IL-8, in human trabecular meshwork (HTM) cells after an oxidative challenge. IL-6 and IL-8 have been linked to the process of cellular senescence. Chronic exposure to these cytokines, which occurs in glaucoma, may damage HTM cells. Rho kinase (ROCK) inhibitor is in a novel class of intraocular pressure reducing drugs. The purpose of this study was to determine if ROCK inhibitor influences IL-6 and IL-8 mRNA expression in HTM cells.
Primary HTM cell cultures were obtained from three donor corneas (n=3). Cells were used prior to the 7th passage. Cells were serum starved for 24 hours and treated with 300 μM hydrogen peroxide (H2O2) for 3 hours in the presence of 25 μM Y-27632. These cells were compared with cells without Y-27632. Selected mRNAs (IL-6, IL-8, and myocilin) from the cells were analyzed using relative quantitative PCR.
H2O2 increased IL-6 mRNA expression 1.76-3.31-fold. Y-27632 suppressed this increase by 0.83-1.28-fold. IL-8 mRNA was increased 5.96-11.58-fold with H2O2 treatment, and this increase was reduced to 2.43-6.13-fold with Y-27632. The effect of Y-27632 on myocilin mRNA was not consistent and depended on the individuality of donors.
Y-27632 reduced IL-6 and IL-8 mRNA expression following oxidative stress in HTM cells. These results suggest that ROCK inhibitor may protect HTM cells from the cellular senescence process due to pro-inflammatory cytokines associated with glaucoma. ROCK inhibitor may provide an additional benefit other than intraocular pressure reduction in glaucoma patients.
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