Wang Ning, Yuan Kelan, Yang Shuo, Jin Xiuming
Eye Center, The Second Affiliated Hospital Zhejiang University of Medicine, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, China.
J Ocul Pharmacol Ther. 2024 Dec;40(10):659-667. doi: 10.1089/jop.2024.0027. Epub 2024 Oct 9.
This study aimed to investigate the effect of 13- retinoic acid (13- RA) on human meibomian gland epithelial cells (HMGECs) and explore the potential of using this experimental model as an approach for studying meibomian gland dysfunction (MGD). First, HMGECs were cultured with 13- RA at different doses and times, and cell viability and proliferation rates were assessed to determine the appropriate stimulation concentration and time. Subsequently, during the proliferation stage, the expression of proliferation, inflammation, and oxidative stress genes and their products were evaluated. The meibum synthesis capacity was determined during the differentiation stage. Additionally, the peroxisome proliferator-activated receptor gamma () antagonist GW9662 was used as a control to assess the impact of 13- RA on . 13- RA significantly inhibited cell viability and proliferation in a time-dose response manner. Under the stimulation of 2 and 5 μM for 48 h during the proliferation stage, a significant decrease was observed in the expression of cell proliferation markers , antioxidant , and . However, the expression of the pro-inflammatory factors , , , and oxidative stress markers and reactive oxygen species increased. During the differentiation stage, it suppressed meibum synthesis and the expression of meibocyte differentiation-related proteins adipose differentiation-associated protein 4 (), elongation of very long chain fatty acid protein 4 (), sterol regulatory element-binding protein 2 (), and . 13- RA inhibited cell viability, promoted inflammation and oxidative stress, and suppressed meibum synthesis through the pathway. Our study shed light on the effect of 13- RA on HMGECs and provided a promising direction for studying MGD .
本研究旨在探讨13 - 视黄酸(13 - RA)对人睑板腺上皮细胞(HMGECs)的影响,并探索使用该实验模型作为研究睑板腺功能障碍(MGD)方法的潜力。首先,将HMGECs与不同剂量和时间的13 - RA一起培养,并评估细胞活力和增殖率,以确定合适的刺激浓度和时间。随后,在增殖阶段,评估增殖、炎症和氧化应激基因及其产物的表达。在分化阶段测定睑脂合成能力。此外,使用过氧化物酶体增殖物激活受体γ( )拮抗剂GW9662作为对照,以评估13 - RA对 的影响。13 - RA以时间 - 剂量反应方式显著抑制细胞活力和增殖。在增殖阶段用2和5 μM刺激48小时后,观察到细胞增殖标志物 、抗氧化剂 和 的表达显著下降。然而,促炎因子 、 、 的表达以及氧化应激标志物 和活性氧增加。在分化阶段,它抑制睑脂合成以及睑细胞分化相关蛋白脂肪分化相关蛋白4( )、超长链脂肪酸延伸蛋白4( )、固醇调节元件结合蛋白2( )和 的表达。13 - RA通过 途径抑制细胞活力,促进炎症和氧化应激,并抑制睑脂合成。我们的研究揭示了13 - RA对HMGECs的影响,并为研究MGD提供了一个有前景的方向。