骨桥蛋白调控实验性青光眼视网膜小胶质细胞的激活及其机制研究

青光眼是一类以多种因素共同作用最终导致视网膜神经节细胞进行性丢失为特征的不可逆性的致盲眼病，小胶质细胞的激活参与了青光眼视神经病变的病理损害过程。骨桥蛋白（OPN）是神经退行过程中的一种活性介质，其可通过调控小胶质细胞的激活和功能来参与中枢神经系统神经退行性疾病的发病过程，但其是否对青光眼视网膜小胶质细胞的激活具有调控作用及其调控机制如何目前尚未完全阐明。我们前期的研究发现慢性高眼压眼视网膜中OPN的表达增加，且其表达与激活的小胶质细胞的分布密切相关，阻断OPN后，激活的小胶质细胞明显减少。由此本项目将采用大鼠慢性高眼压模型的在体实验和小胶质细胞加压培养的体外实验，进一步研究OPN对实验性青光眼状态下视网膜小胶质细胞激活和功能的影响，同时探讨OPN对实验性青光眼状态下小胶质细胞激活调控作用的重要信号通路，丰富青光眼视神经病变的作用机制，为发掘青光眼的视神经保护方法和治疗靶点提供实验依据。

Glaucoma is a type of irreversible blinding eye disease characterized by a combination of multiple factors that eventually lead to the progressive loss of retinal ganglion cells. The activation of microglia is involved in the pathogenesis of glaucomatous optic neuropathy. Osteopontin (OPN) is an active mediator in the process of neurodegeneration, which can participate in the pathogenesis of neurodegenerative diseases of the central nervous system by regulating the activation and function of microglia. However, it is not yet fully elucidated whether OPN could regulate the activation of microglial cells and what it’s the regulatory mechanism during the glaucomatous optic neuropathy. Our preliminary study found that OPN expression increased in chronic ocular hypertensive retina, and its expression was closely associated with the distribution of activated microglia. After blocking OPN, the activated microglia decreased significantly. Therefore, we will use rat model in vivo with chronic ocular hypertension and retinal microglial cells culture in vitro under the pressure condition to study the effect of OPN on the retinal microglia activation and function in experimental glaucoma condition. At the same time, we will further explore the important signaling pathway of OPN for the regulation of microglia activation in experimental glaucoma condition. The expected results of this project will enrich the glaucomatous optic nerve damage mechanisms, and provide the experimental evidences for excavating the treatment method and target of neuroprotection.