去铁胺对慢性高眼压青光眼模型鼠视神经保护作用的研究

青光眼是全球第一位的不可逆性致盲性眼病，其临床特征是选择性、进行性视网膜神经节细胞的死亡。一直以来，谷氨酸浓度升高引起的兴奋性细胞毒性学说被认为是青光眼视网膜神经节细胞大量丢失的关键原因之一。新近的研究表明，谷氨酸引起的细胞兴奋毒性是一种类似于“铁死亡”的氧化应激过程。本研究团队的前期研究结果显示应用铁离子螯合剂能有效减低谷氨酸对视网膜神经节细胞的毒性损伤。基于以上发现，本研究拟从体内和体外两个方面系统探讨谷氨酸-铁离子代谢通路在慢性青光眼模型大鼠发病中的作用，以明确青光眼视网膜神经节细胞存在着类似于“铁死亡”的氧化应激损伤。同时，研究特异性铁离子螯合剂去铁胺（DFO）对谷氨酸-铁离子代谢通路的调控作用及其可能的线粒体介导机制，以明确DFO在慢性青光眼模型鼠中的神经保护作用。进一步阐明青光眼的发病机制，为青光眼的铁离子干预治疗提供可靠的理论依据。

As the first blindness-leading disease, glaucoma is characterized as selective and progressive loss of retinal ganglion cells. Although glutamate induced excitotoxicity has long been regarded as one of the key causes of retinal ganglion cell loss, recent studies have further reported that glutamate induced excitotoxicity is an oxidative stress similar to “Ferroptosis”. Our previous data have proved that using an iron chelator significantly reduced the damages caused by overdose application of THA in retinal ganglion cell culture. In the present study, it is investigated in vivo and in vitro how glutamate-iron metabolism pathway participates in the pathogenesis of glaucoma in a chronic glaucoma model of rats to elucidate an oxidative damage similar to “Ferroptosis” occurred during the retinal ganglion cell loss in glaucoma. Meanwhile, neuroprotective effects of deferoxamine （DFO） by modulating the glutamate-iron metabolism pathway are observed and the underlying mechanisms are also investigated. The results of this project will help to further understand the pathogenesis of glaucoma and to provide reliable theoretical evidence for the iron intervention therapy in glaucoma.