青光眼是全球第二位致盲性眼病，以进行性视网膜神经节细胞（RGC）死亡与轴突变性以及特异性视野缺损为主要特征的慢性视神经病变。目前认为RGC损害机制包括氧化应激、轴突运输障碍、营养因子缺乏和神经炎症等，但其发病机制尚不够清楚。我们发现，发育期和视神经损伤模型视网膜中miR-29家族的表达量降低，Plexins表达量却增多。PC12过表达miR-29发现，下调Plexin A4蛋白表达量，激活Akt-mTOR信号通路。诱导多能干细胞（iPS）定向分化神经元过程中转染miR-29抑制剂，发现神经元分化效率更高、存活更久。鉴于此，我们拟联合基因修饰鼠和原代RGCs、iPS分化神经元，进行miR-29家族在视网膜神经发育以及视神经损伤后修复再生中的功能研究，探索和验证新的靶基因，明确其调控信号通路。尝试通过调控miR-29的表达而治疗神经变性疾病的可能性及可行性，为开发诊疗新方法提供重要科学依据。

Glaucoma, the second leading cause of blindness in the world, is a chronic optic neuropathy characterized by progressive retinal ganglion cell (RGC) axons degeneration and death leading to distinctive visual field defects. Although the pathogenesis of glaucoma is still largely unknown, it is hypothesized that RGCs become damaged through various mechanisms, including oxidative stress, excitotoxicity, defective axonal transport, trophic factor withdrawal, and neuroinflammation. Our preliminary study, observed that miR-29 family decreased significantly in development and optic nerve injury model, whereas increased Plexins expression in the retina. Overexpression of miR-29 into PC12 cells, observed reduced protein levels of Plexin A4 and activation of Akt-mTOR pathway. During induced pluripotent stem cells (iPSCs)-derived neuronal cells, we also observed that the antagomir-29 improved neuronal differentiation efficiency and maintained longer survive. Consequently, we intended to combine the genetically-modified mice, primary RGCs and iPSCs-derived neurons, exploring the biological functions of miR-29 family in the retinal development and restoration and regeneration after optic nerve injury. Aims to discover new target genes and determine the signaling pathways. Attempts to study the possibility and feasibility for the treatment of neurodegenerative diseases by targeting to miR-29 provide an important scientific basis for the development of new methods of diagnosis and treatment.