Ji Jian-Zhong, Elyaman Wassim, Yip Henry K, Lee Vincent W H, Yick Leung-Wah, Hugon Jacques, So Kwok-Fai
Department of Anatomy, The University of Hong Kong, Hong Kong, China.
Eur J Neurosci. 2004 Jan;19(2):265-72. doi: 10.1111/j.0953-816x.2003.03107.x.
We examined the neuroprotective effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cells (RGCs) in a rat glaucoma model with increased intraocular pressure (IOP) and studied the CNTF-mediated activation of Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Elevated IOP was induced by laser photocoagulation of the episcleral and limbal veins. The survival of RGCs was studied using Fluoro-Gold labelled in ocular hypertensive eyes with or without CNTF intravitreal injection. Immunochemical staining and immunoblot analysis for CNTF and phosphorylated STAT3 (pSTAT3) were performed. There was a significant and progressive loss of RGCs in the retinas following the induction of elevated IOP. A single intravitreal injection of 2 microg in 2 microL CNTF significantly protected RGCs up to 4 weeks. pSTAT3 was only transiently expressed in ocular hypertensive eyes. However, in eyes treated with CNTF, pSTAT3 was observed up to 2 weeks after the induction of elevated IOP. In ocular hypertensive eyes, CNTF-positive cells were found in the inner nuclear layer (INL), and there was a transient increase in the pSTAT3 cells in the ganglion cell layer and INL. Immunoblots showed that STAT3 was transiently phosphorylated after IOP increase, but with an injection of CNTF, pSTAT3 protein was observed up to 2 weeks after hypertensive glaucoma induction. Laser-induced chronic ocular hypertension in rats resulted in the death of RGCs and a transient activation of STAT3 in the retina. Intravitreal injection of CNTF showed a significant protection of RGCs, and the JAK-STAT signalling could be one of the important pathways that underlie the mechanism of CNTF neuroprotection in this rat glaucoma model.
我们在眼压升高的大鼠青光眼模型中研究了睫状神经营养因子（CNTF）对视网膜神经节细胞（RGCs）的神经保护作用，并探讨了CNTF介导的Janus激酶/信号转导及转录激活因子（JAK-STAT）通路的激活情况。通过激光光凝巩膜上静脉和角膜缘静脉诱导眼压升高。使用荧光金标记法研究了在眼压升高的眼中，有无玻璃体内注射CNTF时RGCs的存活情况。对CNTF和磷酸化STAT3（pSTAT3）进行了免疫化学染色和免疫印迹分析。眼压升高后，视网膜中的RGCs出现显著且逐渐的丢失。在2微升中单次玻璃体内注射2微克CNTF可在长达4周的时间内显著保护RGCs。pSTAT3仅在眼压升高的眼中短暂表达。然而，在接受CNTF治疗的眼中，在眼压升高诱导后长达2周仍可观察到pSTAT3。在眼压升高的眼中，在内核层（INL）发现了CNTF阳性细胞，并且在神经节细胞层和INL中pSTAT3阳性细胞有短暂增加。免疫印迹显示，眼压升高后STAT3短暂磷酸化，但注射CNTF后，在高血压性青光眼诱导后长达2周仍可观察到pSTAT3蛋白。激光诱导的大鼠慢性高眼压导致RGCs死亡，并使视网膜中的STAT3短暂激活。玻璃体内注射CNTF显示出对RGCs的显著保护作用，并且JAK-STAT信号传导可能是该大鼠青光眼模型中CNTF神经保护机制的重要途径之一。
