Abstract:
This experiment aimed to investigate the feasibility of cytisine (CYT) in treating eye diseases with ocular topical application. An in vitro cytotoxicity test, a hen\'s egg test-chorioallantoic membrane (HET-CAM), and a mouse eye tolerance test were used to fully reveal the ocular safety profiles of CYT. For the efficacy evaluations, CYT\'s effects on cell wound healing, against H2O2-induced oxidative stress damages on cells, and on benzalkonium chloride (BAC)-induced dry eye disease (DED) in mice were evaluated. Results showed that CYT did not show any cytotoxicities at concentrations no higher than 250 μg/ml, while lipoic acid (α-LA) at 250 μg/ml and BAC at 1.25 μg/ml showed significant cytotoxicities within 48 h incubation. The HET-CAM and mouse eye tolerance test confirmed that 0.5% CYT eye drops demonstrated good safety characteristics. Efficacy evaluations showed that CTY significantly promoted cell migration and wound healing. CYT significantly improved cell survival against H2O2-induced oxidative stress damage by reversing the imbalance between the reactive oxygen species (ROS) and antioxidant defense mechanisms. The animal evaluation of the BAC-induced dry eye model revealed that CYT demonstrated a strong treatment effect, including reversing ocular surface damages, recovering corneal sensitivity, and inhibiting neovascularization; HMGB1/NF-κB signaling was involved in this DED treatment by CTY. In conclusion, CYT had strong experimental treatment efficacy against DED with good ocular safety profiles, and it might be a novel and promising drug for DED.
摘要:
本实验旨在探讨红景天碱(CYT)在眼部局部应用治疗眼部疾病中的可行性。体外细胞毒性试验,鸡卵试验-绒毛尿囊膜(HET-CAM),和小鼠眼睛耐受性测试用于充分揭示CYT的眼部安全概况。对于疗效评估,CYT对细胞伤口愈合的影响,对抗H2O2诱导的细胞氧化应激损伤,并对苯扎氯铵(BAC)诱导的小鼠干眼病(DED)进行了评价。结果表明,CYT在浓度不高于250μg/ml时没有任何细胞毒性,而250μg/ml的硫辛酸(α-LA)和1.25μg/ml的BAC在48小时内显示出明显的细胞毒性。HET-CAM和小鼠眼睛耐受性测试证实0.5%CYT滴眼剂表现出良好的安全特性。功效评价显示CTY显著促进细胞迁移和伤口愈合。CYT通过逆转活性氧(ROS)和抗氧化防御机制之间的失衡,显着提高了细胞对H2O2诱导的氧化应激损伤的存活率。对BAC诱导的干眼模型的动物评估表明,CYT表现出强烈的治疗效果,包括逆转眼表损伤,恢复角膜敏感性,并抑制新生血管形成;HMGB1/NF-κB信号参与CTY的DED治疗。总之,CYT对DED具有很强的实验治疗功效,具有良好的眼部安全性,它可能是DED的一种新颖而有前途的药物。