眼压升高是原发性开角型青光眼最重要的危险因素之一。TGF-β2信号通路调控的小梁细胞外基质合成对影响房水流出阻力起到关键作用，其机制尚未明确。研究发现14-3-3zeta与TGF-β受体结合，抑制其泛素化水解，促进TGF-β信号通路传导。我们前期研究发现，在小梁细胞中下调14-3-3zeta表达，抑制了TGF-β2诱导的细胞外基质蛋白FN表达上调。因此我们推测小梁细胞中14-3-3zeta可能通过与TGF-β受体结合，影响其泛素化，调控细胞外基质合成。本课题将以14-3-3zeta为靶点，以TGF-β2诱导的人小梁细胞模型和大鼠高眼压模型为研究对象，通过体内外干预14-3-3zeta表达，从细胞和整体水平研究14-3-3zeta对TGF-β2信号通路调控的细胞外基质合成和房水外流的影响。结果将进一步阐明14-3-3zeta在青光眼发病机制中的作用，为降眼压治疗提供新的靶点和思路。

Elevated intraocular pressure is the one of the primary risk factors contributed to the onset of POAG. Extracellular matrix (ECM) of trabecular meshwork (TM) cells regulated by TGF-β2 signaling pathway plays a key role in aqueous humor outflow, however the specific mechanisms are not fully understood. Recent reports show that 14-3-3zeta prohibits TGF-β receptor form ubiquitination, and promotes the transduction of TGF-β signaling pathway. Our previous study demonstrated that silencing of 14-3-3zeta inhibited up-regulation of FN induced by TGF-β2. Thus, we speculate that 14-3-3zeta might affect ubiquitination of TGF-β receptor by interaction with it, and in this way, regulate the synthesis of ECM in TM cells. In this study, we focus on the role of 14-3-3zeta in the mechanism by which it regulates the TGF-β2 induced synthesis of ECM and IOP elevation in vitro and vivo. This study will not only elucidate the function of 14-3-3zeta in pathogenesis of glaucoma, but also provide a new target and insight into the treatments.