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Abstract #46863 Published in IGR 13-3
Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells
Ammar DA; Kahook MYMolecular Vision 2011; 17: 1806-1813
See also comment(s) by Tin Aung •
Purpose: We investigated the potential short and long-term effects in cultured human rabecular meshwork (TM) cells of various topical glaucoma formulations containing different preservatives. Methods: We tested the fixed combination medications 0.004% travoprost plus 0.5% timolol preserved with either 0.015% benzalkonium chloride (BAK; DuoTrav(registered trademark)), or with 0.001% polyquad (PQ; DuoTrav(registered trademark) BAK-free); and 0.005% latanoprost plus 0.5% timolol preserved with 0.020% BAK (Xalacom(registered trademark)). Also tested was a range of BAK concentrations (0.001%-0.020%) in balanced salt solution (BSS). Cells were treated for 25 min at 37 (degrees)C with solutions diluted 1:10 and 1:100 to mimic the reduced penetration of topical preparations to the anterior chamber. The percentage of live cells was determined mmediately after treatment through the uptake of the fluorescent vital dye calcein-AM. To determine any long-term ffects, we assayed release of matrix metalloproteinase 9 (MMP-9) and apoptosis 24 h after treatments.Results: BAK demonstrated a dose-dependent reduction in TM cell viability, ranging from 71(plus or minus)5% live cells at 0.001% BAK (diluted 1:10) to 33(plus or minus)3% live cells at 0.020% BAK (diluted 1:10). Travoprost (0.004%) plus 0.5% timolol preserved with 0.015% BAK had statistically fewer live TM cells (79(plus or minus)7%) than the same preparation preserved with 0.001% polyquad(registered trademark) (PQ; 93(plus or minus)1%; p<0.001). Latanoprost plus timolol preserved with 0.020% BAK (29(plus or minus)9% live cells) was similar to the 0.020% BAK (33(plus or minus)3%) treatment. However, travoprost plus timolol preserved in 0.015% BAK had significantly more live cells (83(plus or minus)12%) than the 1:10 dilution of 0.015% BAK (49(plus or minus)10%). We also found 0.020% BAK (diluted 1:100) resulted in elevated levels of extracellular MMP-9 at 24 h. Conclusions: These results demonstrate that the substitution of the preservative BAK from topical ophthalmic drugs results in greater in vitro viability of TM cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic BAK effects. BAK treatment appeared to cause elevated levels of MMP-9, a matrix metalloproteinase implicated in the pathogenesis of glaucoma.
M. Y. Kahook. University of Colorado Hospital Eye Center, University of Colorado Denver, Department of Ophthalmology, Aurora, CO, United States.
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
