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Jie Shen, William Chang, Ronnie Nie, Sumit Kumar, Iona D Raymond; The effect of IOP-lowering eyedrops and their excipients on human corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5626.
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© ARVO (1962-2015); The Authors (2016-present)
To compare the cytotoxic effect of four marketed IOP-lowering eyedrops, including Lumigan® unit dose (UD), Ganfort® UD, Monoprost®, Travatan® preserved with polyquaternium-1 (PQ), and selected excipients in these products, including propylene glycol (PPG), PQ, and macrogolglycerol hydroxystearate (MGHS40).
Human corneal epithelial cells were grown on filters to a multi-layered stratification. Test solutions were applied to the apical side of the cell layers. Commercial products were used as supplied. PPG, PQ, and MGHS40 were tested at the same concentration and pH as present in commercial products. Following a 42-hour incubation period, cell viability was determined for all treatment arms using the standard MTT assay. Percent cell viability relative to control was calculated using the optical density values obtained for each treatment arm. Hematoxylin and eosin staining was performed to examine morphology of cell layers post all treatments. In addition, immunostaining for cellular proliferation marker (Ki67) and proteasomal marker (ubiquitin) was performed on transverse sections from the corneal culture.
Cell viability comparison post incubation demonstrated tolerability of the marketed products in the order of Ganfort UD > Lumigan UD > Travatan preserved with PQ > Monoprost. Consistent with this observation, MGHS40, an excipient in Monoprost, was the least tolerated when compared to PPQ and PG, excipients in Travatan. PPG and PQ individually also decreased cell viability. Immunostaining results supported cell viability data, with Ganfort UD and Lumigan UD exhibiting the healthiest morphology, inclusive of robust Ki67 immunoreactivity, as expected for healthy proliferating corneal cells, and low ubiquitin immunoreactivity. In contrast, Monoprost and MGHS40 treated cultures showed loss of DAPI stained nuclei, lower Ki67 and elevated ubiquitin expression levels compared to other treatment groups.
Ganfort UD and Lumigan UD showed little potential of cytotoxicity on cultured human corneal epithelial cells, while Travatan preserved with PQ showed some degree of cytotoxicity. Monoprost, an unpreserved latanoprost eye drop, showed more corneal toxicity compared to the other products, most likely due to its excipient MGHS40, which produced a similar level of cytotoxicity when tested alone.
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