青光眼是首位不可逆性致盲性眼病。研究表明，原发性开角型青光眼可能是一类由病理性高眼压导致的、同时累及视网膜和中枢神经系统的跨神经元变性疾病，但是其发病机制仍然不明了。本团队最近发现鼠视网膜神经节细胞（RGCs）和中枢神经元中均存在sigma2受体和Aβ的表达，sigma2受体特异性配体DKR1516可以显著减少急性高眼压诱导的鼠RGCs死亡。为了探讨DKR1516的作用机制，本研究拟从体外及体内实验两方面研究慢性高眼压青光眼模型大鼠RGCs损伤与中枢外侧膝状体、视放射、视皮质损伤的相关性，及sigma2/RAGE/Aβ信号通路在青光眼发病中的调控机制。探讨DKR1516对sigma2/RAGE/Aβ信号通路的调控机制，及对青光眼模型鼠RGCs和中枢视路神经元的保护作用。最终明确DKR1516通过调控sigma2/RAGE/Aβ信号通路对青光眼神经保护作用的机制，为青光眼的治疗提供新的途径。

Glaucoma is a worldwide leading cause of irreversible vision loss and blind. According to the latest research, primary open-angle glaucoma caused by pathological intraocular pressure may actually be a class of trans-neuronal degenerative diseases impacting the retina and central nerve system at same time. However, the molecular mechanisms remain unclear. Recently our team found the expression of sigma2 receptor and Aβ in retinal ganglion cells (RGCs) of rats and mice. And DKR1516 which is the specific ligand of sigma2 receptor, can significantly reduce the death of RGCs in acute ocular hypertension mouse model. To investigate the mechanism of DKR1516, at first, we are going to investigate the correlation between the RGCs damage of chronic high intraocular pressure rat model and the damage of central lateral geniculate body, optic radiation, visual cortex, as well as regulation and mechanism of sigma2/RAGE/Aβ pathway on glaucoma pathogenesis in vivo and in vitro. Secondly we are going to explore the regulating mechanism of DKR1516 on sigma2/RAGE/Aβ signal pathway, and protective effects on RGCs of glaucoma rat model as well as central visual pathway neuron. Ultimately we will demonstrate the protective mechanism of DKRP1516 by regulating sigma2/RAGE/Aβ signal pathway on glaucoma optic nerve and central visual pathway neurons. Our research may provide a new approach for neuroprotective treatment of glaucoma in the future.