局部眼用前列腺素类似物和防腐剂对角膜上皮细胞的体外毒性。

In vitro toxicity of topical ocular prostaglandin analogs and preservatives on corneal epithelial cells.

机构信息

Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.

出版信息

J Ocul Pharmacol Ther. 2010 Jun;26(3):259-63. doi: 10.1089/jop.2010.0003.

DOI:10.1089/jop.2010.0003

PMID:20565312

Abstract

PURPOSE

To determine the effect of 4 formulations of commercially available prostaglandin analogs (PGAs) on human corneal epithelial cells in vitro.

METHODS

The test solutions (PGAs) examined were tafluprost 0.005% with 0.010% benzalkonium chloride (BAK), travoprost 0.004% with 0.015% BAK, travoprost 0.004% with sofZia, and latanoprost 0.005% with 0.020% BAK. Also tested independently were the 4 respective BAK or sofZia concentrations related to each PGA. Balanced salt solution (BSS) was used as the live control, and a fixative solution containing 70% methanol and 0.2% saponin was used as the dead control. Immortalized human corneal epithelial cells were exposed to test or control solution for 25 min at 37 degrees C and 5% CO(2). A live/dead assay was used to measure the toxicity of the PGAs.

RESULTS

The percentage of live cells in the PGA groups ranged from 2% to 72% of the BSS group (live control). The PGA with the highest relative live cell percentage, at 72% of the live control, was travoprost with sofZia. The next highest PGA, exhibiting 14% live cells, was the formulation of travoprost containing BAK. The other 2 PGAs, tafluprost and latanoprost, had few surviving cells, with 3% and 2% live cells, respectively. The BAK concentrations exhibited 4%, 3%, and 3% for the 0.01%, 0.015%, and 0.02% concentrations, respectively. The stand-alone sofZia cell survival was 68% of the live control.

CONCLUSIONS

All 4 PGA formulations tested demonstrated significantly more toxicity in human corneal epithelial cells than the live control, but there were significant differences among the PGAs. Travoprost with sofZia exhibited the least toxicity, followed by travoprost with BAK, and then tafluprost and latanoprost. The stand-alone preservative systems were also tested and showed similar survival percentages to each respective PGA. The true clinical implications of these findings require further investigation.

摘要

目的

研究市售 4 种前列腺素类似物（PGAs）制剂对体外人角膜上皮细胞的影响。

方法

检测的试验溶液（PGAs）分别为含有 0.010%苯扎氯铵（BAK）的他氟前列素 0.005%、含有 0.015%BAK 的曲伏前列素 0.004%、含有 sofZia 的曲伏前列素 0.004%和含有 0.020%BAK 的拉坦前列素 0.005%。同时，分别检测与每种 PGA 相关的 4 种相应 BAK 或 sofZia 浓度。平衡盐溶液（BSS）作为活细胞对照，含 70%甲醇和 0.2%皂角苷的固定溶液作为死细胞对照。将永生化人角膜上皮细胞暴露于试验或对照溶液中，在 37°C 和 5%CO2 下孵育 25 分钟。采用死活检测法测定 PGAs 的毒性。

结果

PGA 组的活细胞百分比范围为 BSS 组（活细胞对照）的 2%至 72%。具有最高相对活细胞百分比（活细胞对照的 72%）的 PGA 是含有 sofZia 的曲伏前列素。下一个最高的 PGA，表现出 14%的活细胞，是含有 BAK 的曲伏前列素制剂。其他 2 种前列腺素，他氟前列素和拉坦前列素，存活细胞较少，分别为 3%和 2%。BAK 浓度分别为 0.01%、0.015%和 0.02%时为 4%、3%和 3%。独立的 sofZia 细胞存活率为活细胞对照的 68%。

结论

所有 4 种测试的 PGA 制剂在人角膜上皮细胞中的毒性均明显高于活细胞对照，但 PGA 之间存在显著差异。含有 sofZia 的曲伏前列素表现出最低的毒性，其次是含有 BAK 的曲伏前列素，然后是他氟前列素和拉坦前列素。单独的防腐剂系统也进行了测试，与各自的 PGA 具有相似的存活百分比。这些发现的真正临床意义需要进一步研究。