特异性Rho蛋白抑制剂C3对大鼠急性高眼压模型的神经保护作用及机制研究

神经保护在青光眼的治疗上意义重大，但目前仍十分缺乏针对青光眼性视神经损害的有效治疗。前期工作表明，外酶C3转移酶（C3，Rho蛋白的特异性抑制剂）除有降眼压作用外，还显示了明显促进轴突生长的神经保护作用。其作用机制可能通过调控RhoA/ROCK通路，解除对促存活蛋白Akt的抑制作用，从而促进神经元存活。在前期工作的基础上，本研究拟通过AAV载体介导的C3基因眼后段表达研究其对非缺血性急性高眼压模型的视神经保护作用，同时研究其作用机制。所采用模型能模拟急性闭角型青光眼所导致的视神经损害过程，是一种接近青光眼视神经损伤发病机理的动物模型。本研究有望为C3治疗青光眼性视神经损害的研发奠定基础。

Neuroprotection of glaucoma is of great significance. But there is still no effective treatment for glaucomatous optic nerve damage. The preliminary work of our group showed that Exoenzyme C3 Transferase (C3, Rho protein inhibitor) had protective effect to promote axonal growth significantly in addition to a lowering intraocular pressure effect. The mechanism may be through regulation of RhoA / ROCK pathway, lifting the inhibition of Akt pro-survival protein, thereby promoting neuronal survival. Based on previous work, this study was designed to study the neuroprotective effect and the mechanism of C3 on acute glaucoma attack model. C3 gene was delivered into rat eyes intravitreally using adeno-associated virus (AAV) vectors. The animal model may simulate the process of optic nerve damage in acute angle-closure glaucoma, is close to the glaucoma pathogenesis of optic nerve damage. This study will lay the foundation for the treatment of glaucoma by C3.