视网膜节细胞（RGC）在加压损伤早期存在程序性坏死，但其内在分子调控机制目前仍不清楚。我们预实验提示受体相互作用蛋白3（RIP3）介导RGC程序性坏死，其磷酸化是重要的促发事件，根据基因芯片结合前人文献筛选到促/去磷酸化候选蛋白（Rps6k和Dusp19）可能与RIP3存在相互作用。故本项目首先拟确定RIP3磷酸化是否为Rps6k和Dusp19特异性靶标，进而探索Rps6k和Dusp19失平衡对RIP3磷酸化的调控作用，最后研究MLKL是否为RIP3磷酸化介导RGC程序性坏死的下游分子。本项目拟用形态学、细胞生物学和分子生物学等多方法探索以上科学问题，并通过动物实验加以验证。本研究将进一步阐明RIP3介导RGC程序性坏死通路中的上下游调控机制，寻找干预RGC程序性坏死的关键作用靶点，从而减少通过程序性坏死死亡的RGC，为加压诱导的RGC损伤疾病（例如青光眼等）治疗提供理论依据。

There exists necroptosis in retinal ganglion cells (RGCs) following high intraocular pressure at early stage. However, the molecular mechanism is still unclear. Our previous study suggested that receptor interacting protein 3 (RIP3) was involved in RGCs necroptosis, and its phosphorylation was considered as one of the important initial cellular event. Our group has screened the promote/dephosphorylated candidate proteins (Rps6k and Dusp19), which probably bind to RIP3. Therefore, our proposal first plans to identify whether Rps6k and Dusp19 are specific targets for RIP3 phosphorylation, then explore modulation on RIP3 phosphorylation of the Rps6k and Dusp19. Finally study whether mixed lineage kinase domain-like protein (MLKL) is the downstream molecule of RIP3 phosphorylation mediated RGCs necroptosis. Our proposal plans to research upon scientific questions by using morphology, cellular biology and molecular biology, etc. different methods, and convinced by animal models in vivo. Our research will further elucidate the possible upstream and downstream modulation mechanism on RGCs necroptosis of RIP3, find the key intervene targets on RGCs, which will reduce the number of necroptosis cells, and afford the fundamental theory basis in treatment of RGCs injury related diseases (such as acute glaucoma) following high intraocular pressure.