视网膜神经节细胞骨架变化和凋亡是青光眼视神经损伤的重要机制之一。Rho GTP酶是重要的细胞骨架和凋亡调控因子。我们前期研究发现地塞米松作用能引起动物体内视网膜神经节细胞RhoA表达升高。现推测Rho GTP酶蛋白家族可能直接参与调控视网膜神经节细胞骨架和凋亡，在青光眼视神经损伤修复机制中起重要作用。基于目前Rho GTP酶在青光眼视网膜神经节细胞中的研究多局限于RhoA及下游激酶ROCK的现状,本课题拟在过氧化氢诱导的神经节细胞骨架变化和凋亡模型中,系统研究Rho GTP酶家族代表(RhoA/Rac1/Cdc42)及其下游信号通路的表达变化,探讨Rho GTP酶网络式调控神经节细胞骨架和凋亡机制;同时在青光眼动物模型中利用RNA干扰技术下调RhoA蛋白表达,观察RhoA蛋白对神经节细胞再生的影响。结果有望进一步阐明青光眼视网膜神经节细胞损伤机制，为视神经保护基因治疗奠定基础。

Alteration of retinal ganglion cell cytoskeleton and apoptosis are important in the pathogenesis of glaucomatous optic nerve damage. Rho GTPase plays an important role in regulation of cytoskeletal system and cells apoptosis. Our previous study found the RhoA protein was elevated in mice retinal ganglion cells after dexamethasone treatment. Now we speculate the Rho GTPase family may be directly involved in the mechanisms of glaucomatous optic nerve injury and recovery from elevated intraocular pressure (IOP). Current study on retinal ganglion cells limits much to the RhoA and downstream ROCK. Consequently we aim to systematically study the RhoA\Rac1\ Cdc42 and their key downstream signaling elements in hydrogen peroxide induced cells, meantime we explored the use of RhoA siRNA（siRhoA）to protect the optic nerve through down regulation of RhoA gene and protein expression. The results are expected to expound the mechanism of glaucoma optic nerve damage, and lay the ground work for gene therapy in glaucoma neuroprotection.