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Yi Wei, Penny A Asbell, Natalia Perekhvatova, Anton Petrov; Role of SKQ1 On Inflammatory Responses Associated With Ocular Surface Disease: A Cell Culture Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1184.
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© ARVO (1962-2015); The Authors (2016-present)
SKQ1 (Visomitin) is a novel mitochondrial-targeted anti-oxidant that holds promise for treatment of the ocular surface inflammation. The goal of this study is to determine the potential role of SKQ1 as an anti- inflammatory drug for the treatment of ocular surface inflammation, such as that seen in dry eye disease.
This study employed an established human conjunctival epithelial (HCjE) cell culture model. In brief, HCjE was sensitized with pro-inflammatory cytokines TNF-α and IL-1β to create quantifiable inflammation. Varying concentrations of SKQ1 (0-400 nm) were added to evaluate whether SKQ1 could down regulate an inflammatory response of surface epithelial cells. Morphologic abnormities were examined microscopically. Standard MTT assays were performed and the toxic concentration of SKQ1 that caused HCjE to grow 50% as well as the cells with the culture medium-only controls (TC50) was determined. The production of an inflammatory biomarker, prostaglandin E2 (PGE2), was measured in the culture medium after 24- or 48-hours of SKQ1 treatment.<br />
SKQ1 showed no apparent toxicity until the concentration approached 250 nM. Increasing concentrations of SKQ1 above this level caused cellular morphologic changes and cell death, the TC50 was determined to be 317 nM. SKQ1 at concentrations below 300 nM can effectively reduce the PGE2 production in HCjE as observed at 24 hours of treatment. Such an inhibitory effect on PGE2 production was further noted after 48 hours of SKQ1-treatments at SKQ1 concentrations below 50 nM. The inhibition is apparently SKQ1 dose- and treatment time-dependent. At concentrations higher than 300 nM (24-hour) or 50 nM (48-hour), SKQ1 displays significantly cytotoxicity, therefore the inhibitory effect on PGE2 production decreases and cannot be accurately assessed.
Our results demonstrate that SKQ1 can be safely applied to the conjunctival epithelial cells up to a concentration of 300 nM (181 ng/mL) for 24-hours. The data provide support for SKQ1 as a promising new anti-inflammatory therapy for inflammatory conditions of the ocular surface such as in dry eye disease.
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