有研究显示急性高眼压后早期视网膜节细胞（RGC）出现程序性坏死，受体相互作用蛋白-3（RIP-3）在RGC的程序性坏死分子通路中发挥了重要介导作用，进一步研究发现降低RIP-3的介导作用，并不能完全抑制RGC的程序性坏死，这提示仍有某种未知的分子通路也参与死亡过程。我们的预实验结果提示Calpain-AIF-Chromatinolysis通路可能参与了急性高眼压后早期非"RIP-3"介导的RGC程序性坏死。本项目拟对该假说进行验证，并探索该通路中的关键启动分子Calpain是否受到上游"Pin-1-Calpastatin磷酸化"两个分子层次的负调控。该假说的实验验证将有助于完善急性高眼压后大鼠RGC走向程序性坏死的分子机制，为急性高眼压患者早期视神经保护的药物治疗机理和药物干预靶点提供理论支持和依据。

Our previous research suggest that necroptosis occurs in retina ganglion cells (RGCs) at the early stage following acute high intra-ocular pressure(aHIOP), receptor interacting protein 3 (RIP3) may play a key role in RGCs necroptosis. However, There are still exist some necroptosis RGCs after knockdown rip3 gene expression using the method of RNAi in our further research. It indicates that an unknown molecular pathway may exist to participate in this process. Therefore, this project try to explore whether the molecular pathway named "Calpain-AIF-Chromatinolysis" participate in non-RIP3 induced necroptosis in RGCs following aHIOP. Based on our previous study and possible "Calpain-AIF-Chromatinolysis" molecular pathway has beed veiled, we further try to demonstrate that whether the key endogenous molecular named calpain in "Calpain-AIF-Chromatinolysis" pathway is regulated by Pin1 via calpastatin phosphorylation. Our research will improve the understanding of molecular mechanism of RGCs necroptosis at the early stage of aHIOP, and provide some theoretical evidence or drug development target to treat with patients suffering in acute high intra-ocular pressure.