HtrA2/Hax-1信号轴调控线粒体内稳态影响RGCs凋亡的分子机制

线粒体内稳态失衡在视网膜神经节细胞（RGCs）凋亡中发挥着重要作用。文献报道，HtrA2/Hax-1信号轴参与了线粒体内稳态调控；同时，课题组预实验发现，HtrA2/Hax-1与视神经损伤后RGCs凋亡存在关联。基于此，我们提出假说：HtrA2/Hax-1信号轴可通过调控线粒体内稳态，进而影响RGCs凋亡过程。课题组首先在体内外RGCs凋亡模型中，明确HtrA2/Hax-1信号轴在RGCs凋亡中发挥的作用；在此基础上，进一步分析HtrA2/Hax-1信号轴对钙离子浓度、活性氧表达、线粒体膜电位等RGCs线粒体内稳态平衡指标的调控作用；最后，在整体视神经损伤诱导的RGCs凋亡模型中，通过干预HtrA2/Hax-1信号轴，观察能否通过促进RGCs线粒体回归内稳态平衡，进而抑制RGCs凋亡并改善视功能。课题研究结果将为视神经损伤相关疾病的治疗提供理论依据和新的分子靶点。

Imbalance of mitochondrial homeostasis plays a pivotal role in retinal ganglion cells (RGCs) apoptosis. Previous studies reported that HtrA2/Hax-1 signaling participated in imbalance of mitochondrial homeostasis; Meanwhile, we have found that HtrA2/Hax-1 signaling involved in RGCs apoptosis after optic nerve injury. Therefore, we speculated that HtrA2/Hax-1 signaling could affect RGCs apoptosis via regulation of mitochondrial homeostasis. We aim to determine the involvement of HtrA2/Hax-1 signaling in RGCs apoptosis in vivo and in vitro; investigate the effect of HtrA2/Hax-1 signaling in mitochondrial homeostasis (include calcium ion concentration, reactive oxygen species expression, mitochondrial membrane potential); evaluate the effect of HtrA2/Hax-1 signaling intervention on mitochondrial homeostasis and RGCs apoptosis in the RGCs apoptosis model induced by optic nerve injury. All the data may support basic theory and molecular target for therapy in optic nerve injury-related diseases.