青光眼药物和防腐剂对培养的人眼小梁网和非色素睫状上皮细胞系的影响。
Effects of glaucoma medications and preservatives on cultured human trabecular meshwork and non-pigmented ciliary epithelial cell lines.
机构信息
Rocky Mountain Lions Eye Institute, Department of Ophthalmology, University of Colorado Denver, Aurora, CO 80045, USA.
出版信息
Br J Ophthalmol. 2011 Oct;95(10):1466-9. doi: 10.1136/bjophthalmol-2011-300012. Epub 2011 May 20.
AIMS
We investigated the potential cytotoxicity of various topical ophthalmic glaucoma formulations containing different preservatives in cultured human trabecular meshwork (TM) and non-pigmented ciliary epithelial (NPCE) cell lines.
METHODS
We tested 0.004% travoprost preserved with either 0.015% benzalkonium chloride (BAK), sofZia or 0.001% Polyquad (PQ); and 0.005% latanoprost preserved with 0.020% BAK. We also tested a range of BAK concentrations in balanced salt solution (BSS). TM cells were treated for 10 min at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. Viability was determined by the uptake of the fluorescent vital dye calcein-AM (n = 6).
RESULTS
BAK solutions (diluted 1:10) demonstrated a dose-dependent reduction in cell viability in both cell types (TM and NPCE). With a 1:10 dilution of 0.020% BAK, there were significantly more living NPCE cells (89 ± 6%) than TM cells (57 ± 6%; p < 0.001). 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 with 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%).
CONCLUSIONS
These results demonstrate that substitution of BAK from topical ophthalmic drugs results in greater viability of cultured TM cells, the cells involved in the conventional outflow pathway. Cultured NPCE, responsible for aqueous inflow, appear more resilient to BAK.
目的
我们研究了含有不同防腐剂的各种局部眼科青光眼制剂在培养的人眼小梁网(TM)和非色素睫状上皮(NPCE)细胞系中的潜在细胞毒性。
方法
我们测试了 0.004%曲伏前列素分别用 0.015%苯扎氯铵(BAK)、sofZia 或 0.001%聚季铵盐(PQ)保存,以及 0.005%拉坦前列素用 0.020% BAK 保存。我们还在平衡盐溶液(BSS)中测试了一系列 BAK 浓度。TM 细胞在 37°C 下用稀释 1:10 的溶液处理 10 分钟,以模拟局部制剂对前房的渗透减少。通过荧光活细胞染料 calcein-AM 的摄取来确定细胞活力(n = 6)。
结果
BAK 溶液(稀释 1:10)在两种细胞类型(TM 和 NPCE)中均表现出剂量依赖性的细胞活力降低。用 0.020% BAK 的 1:10 稀释液,NPCE 细胞的活细胞(89 ± 6%)明显多于 TM 细胞(57 ± 6%;p < 0.001)。在 TM 细胞中,曲伏前列素+BAK 的活细胞数量明显少于曲伏前列素+sofZia(97 ± 5%)和曲伏前列素+PQ(97 ± 6%;p < 0.05)。与 BSS 处理的 NPCE 细胞相比,用 BAK(85 ± 16%)、sofZia(91 ± 6%)或 PQ(94 ± 2%)保存的曲伏前列素的活细胞数量明显减少(p < 0.05)。
结论
这些结果表明,从局部眼科药物中替代 BAK 可导致培养的 TM 细胞(参与传统流出途径的细胞)的活力增加。负责房水流入的培养 NPCE 对 BAK 更具抵抗力。