青光眼是一类以视网膜神经节细胞（RGC)进行性丢失为特征的首位不可逆致盲眼病。防治青光眼的关键是保护和挽救RGC，其中神经保护药物和策略很有希望和前景。然而目前尚无肯定疗效的神经保护药物应用于临床。迫切需要探寻有效的药物和方案。最近报道丙戊酸钠（VPA）可多靶点保护脑神经元。申请人前期研究发现VPA和Shh对青光眼RGC的保护作用均优于BDNF和CNTF，VPA侧重功能保护，Shh以挽救RGC数量为突出，且VPA可提高AAV2-Shh在体外培养RGCs的表达。提示VPA联合AAV2-Shh可望实现优势互补、协同增效的保护作用。为此本课题拟深入研究VPA联合AAV2-Shh挽救慢性高眼压RGC数量和功能的多靶点、协同增效作用及其关键分子与重要信号通路，并探讨VPA多靶点调控关键分子表达的表观遗传机制，以及VPA提高AAV2介导基因表达的分子机制。旨在探寻青光眼神经保护的有效药物和解决方案。

Glaucoma is the first blindness disease in the world which characterized by progressive RGC death. The final goal to glaucoma is to protect RGC to survive. The neuroprotective drug or strategy is the most promising one. However, there is no effective neuroprotective drugs in clinic.It is necessary to seek novel neuroprotective drugs and methods. Recently,it has been reported that valproic acid (VPA) can protect neuron in brain through multiple targets. We have found previously that the neuroprotective effect of VPA or Shh on RGCs in glaucoma is more better than BDNF or CNTF. VPA particularly protected the function of RGCs and Shh mainly rescued the numbers of RGCs. Furthermore, VPA can enhance the gene expression mediated by AAV2-GFP-Shh in the cultured RGCs.These results suggesting that combination of VPA and AAV2-GFP-Shh may achieve complementary and the synergetic protective effect on RGCs in glaucoma. In this study, we study the multiple targets and synergetic protective effects of VPA and AAV2-GFP-Shh on RGCs in Glaucoma, the key elememts and signal tansudction ways during this process, and their epigenetic mechanisms. Moreover, we also study the molecular mechanisms of VPA increasing AAV2-mediated gene expression. The goal of this project is to seek the effective neuroprotection drugs and strategy.