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David A. Ammar, Malik Y. Kahook; Effects of Benzalkonium Chloride-, PolyquadTM-, and sofZiaTM-preserved Glaucoma Medications on Human Trabecular Meshwork and Non-Pigmented Ciliary Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4659.
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We investigated the potential cytotoxicity of various topical ophthalmic glaucoma formulations containing different preservatives in cultured human trabecular meshwork (TM) cells and non-pigmented ciliary epithelial (NPCE) cells.
We tested 0.004% travoprost preserved with either 0.015% benzalkonium chloride (BAK), sofZiaTM, or 0.001% polyquadTM (PQ); and 0.005% latanoprost preserved with 0.020% BAK. Also tested was a range of BAK concentrations (0.001 - 0.020%) in balanced salt solution (BSS). Controls included cells treated with BSS (100% Live) or fixed in 70% methanol (Dead). TM cells were treated for 10 minutes at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. Viability was determined by assaying the uptake of the fluorescent vital dye calcein-AM.
BAK solutions (diluted 1:10) demonstrated a dose-dependent reduction in cell viability in both cell types (TM and NPCE). At the highest concentration of BAK tested (1:10 dilution of 0.020%), there were significantly more living NPCE cells (89 ± 6%) than TM cells (57 ± 6%). In TM cells, travoprost + BAK had statistically fewer live cells (83 ± 5%) than both travoprost + sofZia (97 ± 5%) and travoprost + PQ (97 ± 6%; p < 0.05). Compared to BSS-treated NPCE cells, travoprost had statistically fewer live cells (p < 0.05) when preserved with BAK (85 ± 16%), sofZia (91 ± 6%) or PQ (94 ± 2%). However, these percentages were not significant among the different preservatives.
These results demonstrate that the substitution of BAK from topical ophthalmic drugs results in greater viability of TM cells, the cells involved in maintaining the conventional outflow pathway in vivo. The cells responsible for aqueous inflow, NPCE, appear more resilient to BAK.
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