神经性致盲眼病青光眼累及视网膜网络的输出神经元——神经节细胞(RGC)的功能，造成视觉损伤。我们先前的研究发现，慢性高眼压实验性青光眼视网膜EphB/ephrinB反向信号参与RGC的凋亡。在此动物模型上，我们的预实验结果发现，ephrinA3和EphA4分别在Müller细胞和RGC上的表达显著增强，提示ephrinA3/EphA4信号的激活可能调控Müller细胞和RGC的功能，进而导致RGC的损伤。为此，本课题以慢性高眼压为模型，采用多学科技术，在我们已有研究的基础上，深入研究EphA4/ephrinA3反向信号激活调控Müller细胞谷氨酸转运体功能和胶质化激活的机制，分析其在RGC凋亡中的作用；研究ephrinA3/EphA4正向信号对RGC损伤的机制，并尝试干预该信号对RGC的神经保护作用。本课题的研究成果将为阐明青光眼RGC损伤的机制以及有效地防治青光眼提供理论参考依据。

Glaucoma is one of severe retinal diseases, which is characterized by visual loss due to the apoptotic death of retinal ganglion cells (RGCs), output neurons in the retina. We previously demonstrated that EphB/ephrinB reverse signaling is involved in RGC apoptosis in rat chronic ocular hypertension (COH) experimental glaucoma model. In COH model, our preliminary results showed that the expression of ephrinA3 and EphA4 increased in Müller cells and RGCs respectively, suggesting that activated ephrinA3/EphA4 signaling may modulate the functions of Müller cells and RGCs, thus contributing to RGC apoptosis. In the proposed research, based on our previous studies, we aim to explore the cellular and molecular mechanisms underlying changes in glutamate transporters in Müller cells and Müller cell gliosis due to activation of EphA4/ephrinA3 reverse signaling, and investigate the effects of this signaling on RGC apoptosis in experimental glaucoma, using multi-disciplinary approaches. We will also try to elaborate the cellular and molecular mechanisms underlying RGC apoptosis due to activation of ephrinA3/EphA4 forward signaling in RGCs. Neuroprotective effects of inhibiting ephrinA3/EphA4 forward signaling on RGCs in experimental glaucoma will be further examined. Results to be derived from this study are expected to elucidate roles and mechanisms underlying activated ephrinA3/EphA4 bi-directional signaling induced RGC apoptosis in glaucoma, thus providing potential ways for effective prevention and cure of glaucoma.