AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition(EMT) in human retinal pigment epithelial cells(ARPE-19) in vitro.METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/m L bevacizumab for 12, 24, and 48 h.Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1(ZO-1), vimentin and Notch-1 intracellular domain(NICD) was examined by immunofluorescence.The m RNA levels of ZO-1, α-SMA, Notch-1, Notch-2,Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR). The protein levels of α-SMA,NICD, Hes-1 and Dll-4 expression were examined with Western blot.RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells.Meanwhile, the m RNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The m RNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48 h, and while Dll4 m RNA and protein expression did not change after bevacizumab treatment.CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.
Jing-Jing ZhangSan-Jun ChuXiao-Lei SunTing ZhangWei-Yun Shi
目的探讨在高眼压下对急性闭角型青光眼患者行小梁切除术,术中保持较正常的前房与术后并发症的关系。方法回顾分析了14例(17只眼)急性闭角型青光眼患者,术前应用全身及局部降眼压药物降压治疗后,眼压仍>30 mm Hg,行小梁切除术,术中应用高弹性黏弹剂使整个手术过程中前房基本保持正常深度,切除小梁后,可调节缝线紧密缝合,并记录观察手术效果,对术后早期并发症,特别是术后浅前房、睫状环阻塞性青光眼发生率的改变。结果术后浅前房发生率为5.8%,术后观察6个月,眼压均控制在18 mm Hg以下,无暴发性脉络膜出血、睫状环阻塞性青光眼发生。结论高眼压状态下行青光眼滤过手术,术中采用前房注射高弹性黏弹剂形成前房,加缝巩膜瓣可调节缝线可有效避免术后并发症的发生。
