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Mechanisms of benzalkonium chloride toxicity in a human trabecular meshwork cell line and the protective role of preservative‐free tafluprost
Author(s) -
Chang Caitlin,
Zhang Angela Q,
Kagan Dov B,
Liu Hong,
Hutnik Cindy ML
Publication year - 2015
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.12390
Subject(s) - benzalkonium chloride , viability assay , apoptosis , toxicity , trabecular meshwork , medicine , pharmacology , chemistry , biochemistry , ophthalmology , pathology , glaucoma
Background Benzalkonium chloride ( BAK ) is a controversial ophthalmic preservative because of its prominent side‐effect profile. In this study, we examined the mechanism of BAK toxicity in human trabecular meshwork cells ( HTMC ) and compared the effects of BAK with tafluprost free acid, which is an active form of tafluprost commercially available in a preservative‐free formulation. Methods Primary HTMC were treated with different BAK concentrations over various exposure times. Cell viability was quantified using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenol tetrazolium bromide assay, and apoptosis was measured by enzyme‐linked immunosorbent assay. The cell viability of primary HTMC exposed to various concentrations and times of tafluprost free acid was also determined. Cells were treated with BAK and tafluprost free acid for 30 min at 37°C, and cell viability was again assessed. The effect of BAK on the gap junction protein C onnexin‐43 ( C x43) expression was subsequently examined. Results BAK treatment resulted in a dose‐ and time‐dependent decline in cell viability. Apoptosis increased following BAK treatment. Tafluprost‐free acid treatment did not significantly affect cell viability. Tafluprost co‐treatment with BAK resulted in an increase in cell viability as compared with BAK treatment alone. BAK treatment upregulated C x43 expression in HTMC . Conclusions These results demonstrate that BAK is harmful to the health of cultured HTMC . Tafluprost is both safe and cytoprotective against BAK for these HTMC . The effect of tafluprost on the gap junctions of the HTM should be further investigated.