Porf-2调控EphB3/EphrinB3细胞间信号传导影响视神经损伤后轴突再生的分子机制

尽管视神经损伤修复研究不断取得进展，但视网膜神经节细胞（RGCs）轴突再生效果仍不理想。近年来，EphB/EphrinB介导的星形胶质细胞-RGCs轴突间信号传导逐渐成为轴突再生的研究热点，然而RGCs轴突是如何感受外部细胞信号并将其传递至下游骨架蛋白进而影响轴突再生的机制尚不清楚。最近，我们发现视前区调控因子-2（Porf-2）对轴突生长具有抑制作用，在视神经损伤后RGCs轴突表达上调。进一步研究发现EphrinB3可与Porf-2相互结合，在视神经损伤后两者的表达呈正相关。我们推测视神经损伤后Porf-2可以调控EphB3/EphrinB3细胞间信号传导影响视神经损伤后轴突再生。本项目拟采用细胞生物学和分子生物学等技术，通过体内、外研究对该假说进行深入探索，其成果可以为RGCs轴突再生提供新的标靶和理论依据。

Significant progress has been made in the repairment of optic nerve injury (ONI), however, the efficacy of retinal ganglion cells (RGCs) axonal regeneration is still unsatisfactory. In recent years, EphB/EphrinB-mediated astrocytes-RGCs axonal signaling transduction has gradually become a research hotspot. Nevertheless, it remains unclear how RGCs axons sense the external intercellular signal and transduce it to the downstream cytoskeletons, which leads to the axonal regeneration. Recently, we found that preoptic regulatory factor-2 (Porf-2) has an inhibitory effect on axonal growth and was upregulated in RGCs axons after ONI. Further studies revealed that EphrinB3 could bind with Porf-2, and they had positive correlation post-ONI. Therefore, we proposed that Porf-2 could regulate signal transductions of the EphB3/EphrinB3 intercellular reverse signals in RGCs axons, which affect the axonal growth. Our team plans to employ cellular and molecular biology technology to confirm the above hypothesis in vivo and vitro. This research can provide new targets and theoretical basis for RGCs axonal regeneration research.