青光眼是眼科最常见的不可逆性致盲性眼病，其主要病理特征为视网膜神经节细胞(RGCs)的损伤，但损伤机制尚不明确。申请人已证实Tau寡聚体的神经毒性是导致RGCs损伤的重要新机制。根据中枢神经退行性病变中RNA结合蛋白TIA1可调控Tau寡聚体形成的机制，以及预实验中发现TIA1及其相关蛋白TIAR在RGCs损伤时表达均显著上升、且TIAR能下调RGCs中Tau寡聚体形成的现象，提出假设：在慢性高眼压模型中，TIA1/TIAR调控Tau寡聚体形成而引起RGCs损伤。本研究拟建立体外高压缺氧刺激RGCs环境和体内小鼠慢性高眼压模型，通过体内外干预TIA1与TIAR，研究TIA1调控Tau寡聚体形成的作用机制及其在RGCs损伤和青光眼发生中的作用，并延伸探索小鼠体内靶向抑制TIA1表达治疗慢性高眼压神经损伤的疗效和安全性，该研究有望为青光眼的治疗提供新的靶点和理论基础。

Glaucoma is the most common irreversible blinding eye disease. Its main pathological feature is the damage of retinal ganglion cells (RGCs), but the mechanism of RGCs injury is still unclear. In our previous paper, we have demonstrated that the neurotoxicity of Tau oligomers is an important factor leading to RGCs damage. So Tau oligomer has become a potential target for the treatment of glaucoma. In central neuronal degenerative diseases, RNA binding protein T-cell intracellular antigen-1 (TIA1) can regulate the Tau oligomer formation. In the preliminary experiment, we found that:1)TIA1 and its related protein TIAR was significantly increased in chronic HIOP model 2) in vitro we found TIAR could regulate Tau oligomerization in primary RGCs. Other researchers have found that the TIA1/TIAR can cooperate in pathologic conditions. We, therefore, raise the hypothesis that: in the chronic HIOP model, TIA1/TIAR can induce Tau oligomer formation, and then cause the RGCs damage. In this study we will use the hyperbaric hypoxia model in vitro and the chronic HIOP mice model, to study the mechanism of TIA1 regulation of Tau oligomer formation and its role in RGCs injury, through the intervention of TIA1 and TIAR expression. We will further explore the protective effect of inhibition TIA1 in chronic HIOP model by application of Adeno-associated virus siRNA TIA1. This study is expected to provide a new target and theoretical basis for the treatment of glaucoma.