Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Schepens Eye Research Institute, Massachusetts Eye and Ear; and.
Cornea. 2020 Dec;39(12):1541-1546. doi: 10.1097/ICO.0000000000002506.
Infestation with demodex mites has been linked to the development of chalazion, meibomian gland dysfunction, and blepharitis. An effective treatment is the eyelid application of terpinen-4-ol (T4O), a tea tree oil component. However, T4O is also known to be toxic to nonocular epithelial cells. We hypothesize that T4O toxicity also extends to human meibomian gland epithelial cells (HMGECs).
Immortalized (I) HMGECs were cultured with varying concentrations (1.0%-0.001%) of T4O under proliferating or differentiating conditions up to 5 days. Experimental procedures included analyses of cell appearance, survival, P-Akt signaling, lysosome accumulation, and neutral lipid content.
Our findings show that T4O causes a dose- and time-dependent decrease in the cell survival of IHMGECs. After 15 minutes of exposure to 1% T4O, IHMGECs exhibited rounding, atrophy, and poor adherence. Within 90 minutes of such treatment, almost all cells died. Reducing the T4O concentration to 0.1% also led to a marked decrease in P-Akt signaling and cell survival of IHMGECs. Decreasing the T4O amount to 0.01% caused a slight, but significant, reduction in the IHMGEC number after 5 days of culture and did not influence the ability of these cells to differentiate.
T4O, even at levels 10-fold to 100-fold lower than demodicidal concentrations, is toxic to HMGECs in vitro.
螨虫感染与睑板腺囊肿、睑板腺功能障碍和睑缘炎的发展有关。一种有效的治疗方法是在眼睑上涂抹茶树油的成分——萜品-4-醇(T4O)。然而,T4O 也被认为对非眼部上皮细胞有毒性。我们假设 T4O 的毒性也会扩展到人类睑板腺上皮细胞(HMGEC)。
用不同浓度(1.0%-0.001%)的 T4O 培养永生(I)HMGECs,在增殖或分化条件下培养长达 5 天。实验程序包括细胞外观、存活、P-Akt 信号、溶酶体积累和中性脂质含量的分析。
我们的研究结果表明,T4O 导致 IHMGECs 的细胞存活率呈剂量和时间依赖性下降。暴露于 1% T4O 15 分钟后,IHMGECs 表现出圆化、萎缩和贴壁不良。在这种处理后 90 分钟内,几乎所有的细胞都死亡了。将 T4O 浓度降低到 0.1%也导致 IHMGECs 的 P-Akt 信号和细胞存活率明显下降。将 T4O 量减少到 0.01%,在培养 5 天后会导致 IHMGEC 数量略有但显著减少,但不会影响这些细胞分化的能力。
T4O 即使在比杀螨虫浓度低 10 到 100 倍的水平下,对体外 HMGECs 也是有毒的。