激素性高眼压主要是由于小梁网细胞功能障碍和调亡导致房水流出阻力增加所致，但具体机制尚未阐明。我们前期的研究表明激素处理后小梁网细胞MYOC基因表达显著增高。那么，MYOC编码的myocilin蛋白是否介导激素性高眼压中小梁网细胞的功能障碍甚至凋亡？其机制是什么？以往研究表明myocilin蛋白在果蝇眼中过表达可导致内质网应激（ERS），而我们的前期研究表明ERS参与了激素性高眼压的形成，因此我们提出假设：在激素性高眼压中糖皮质激素作用于小梁网细胞，导致myocilin蛋白大量合成，耗竭了细胞降解蛋白能力，产生ERS，进而导致小梁网细胞功能障碍甚至凋亡。本项目拟采用我们前期研发的载si-RNA纳米微粒，结合基因工程小鼠、质粒载体等工具，通过细胞和动物实验阐明激素性高眼压中myocilin蛋白是导致内质网应激，进而导致小梁网细胞凋亡的关键位点，为寻找防治激素性高眼压的治疗靶点提供科学依据。

In glucocorticoid-induced ocular hypertension, the resistance to aqueous humor outflow through the drainage structure of the trabecular meshwork (TM) is increased, thus elevating IOP. The mechanisms that cause increased outflow resistance in the TM is still unclear. Our previous study reveal that MYOC is highly induced by glucocorticoid in TM cell. So, whether MYOC participate in the mechanisms of glucocorticoid-induced ocular hypertension? And how? Previous study had reported that overexpress of MYOC can activates the endoplasmic reticulum stress (ERS) in Drosophila Eye. Our previous results suggested that ERS participate in the mechanisms of glucocorticoid-induced ocular hypertension. So, we suppose that long-term treatment of glucocorticoid can induced over-expressed myocilin, then can induced endoplasmic reticulum stress in TM cells and cause TM cell apoptosis by activates unfolded protein response. Therefore, in this investigation, we intend to investigate the role of myocilin in glucocorticoid-induced ocular hypertension by combined the use of si-RNA-Nano-corpuscle, MYOC knock-out mice, plasmid vector and so on.