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Malik Y. Kahook, David A. Ammar; Effects of Benzalkonium Chloride- or PolyquadTM-preserved Combination Glaucoma Medications on Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4663.
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We investigated the potential short and long-term effects in cultured human trabecular meshwork (TM) cells of various topical glaucoma formulations containing different preservatives.
We tested the combination medication of 0.004% travoprost plus 0.5% timolol preserved with either 0.015% benzalkonium chloride (BAK) or with 0.001% polyquadTM (PQ); and 0.005% latanoprost plus 0.5% timolol preserved with 0.020% BAK. Also tested was a range of BAK concentrations (0.001 - 0.020%) in balanced salt solution (BSS). Controls included 100% Live (treated with BSS) and Dead (treated with 70% methanol). Cells were treated for 25 minutes at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. The percentage of live cells was determined immediately after treatment through the uptake of the fluorescent vital dye calcein-AM. To determine any long-term effects, we assayed release of matrix metalloproteinase 9 (MMP-9) 24 hours after treatments.
BAK solutions demonstrated a dose-dependent reduction in TM cell viability, ranging from 71 ± 5% live cells at 0.001% BAK (diluted 1:10) to 33 ± 3% live cells at 0.020% BAK (diluted 1:10). Travoprost with timolol preserved with BAK had statistically fewer live TM cells (79 ± 7%) than the same preparation preserved with PQ (93 ± 1%; p < 0.001). Latanoprost with timolol preserved with 0.020% BAK (29 ± 9% live cells) was similar to the 0.020% BAK treatment (33 ± 3%). However, travoprost with timolol preserved in 0.015% BAK had significantly more live cells (83 ± 12%) than the 0015% BAK (49 ±10%). We also found that 0.015% or 0.020% BAK treatment (diluted 1:100) resulted in elevated levels of extracellular MMP-9 at 24 hours.
These results demonstrate that the substitution or removal of the preservative BAK from topical ophthalmic drugs results in greater viability of TM cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic BAK effects. BAK treatment appeared to cause release of elevated levels of MMP-9, a matrix metalloproteinase implicated in the pathogenesis of glaucoma.
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