IL-17A对实验性青光眼视网膜小胶质细胞激活的调控作用研究

青光眼是一类以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损害过程。IL-17A是新近发现的一种细胞因子，其可通过调控小胶质细胞的激活和功能来参与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阐明。我们前期的研究发现IL-17A-/-小鼠慢性高眼压眼视网膜小胶质细胞的激活明显较野生型小鼠减轻，且IL-17A中和抗体能明显减轻野生型小鼠慢性高眼压眼小胶质细胞的激活。由此本项目将采用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IL-17A对实验性青光眼状态下视网膜小胶质细胞激活、极化状态和功能的影响，探讨IL-17A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 an irreversible blinding disease characterized by progressive loss of retinal ganglion cells (RGC). A major pathogenic pathway in glaucomatous RGC degeneration is the activation of microglia. IL-17A is a newly discovered cytokine, which has been shown to participate in the pathogenesis of neurodegenerative diseases by regulating the activation and function of microglia. However, it is not clear whether IL-17A regulates the activation of microglial cells and what is the regulatory mechanism during the course of RGC degeneration in glaucoma. Our preliminary data show that the activation of retinal microglia in IL-17A-/- mice with chronic ocular hypertension was significantly less than that in wild-type mice, and IL-17A neutralizing antibody significantly reduced the activation of microglia in wild-type mice with chronic ocular hypertension. In the proposed study, we will use an in vivo mouse model of chronic ocular hypertension and in vitro retinal microglial cells culture under pressure to study the effect of IL-17A on the retinal microglia activation, the microglia polarization and their roles in experimental glaucoma. In addition, we will explore the signaling pathway of IL-17A for the regulation of microglia activation in experimental glaucoma. The study finding will enrich the understanding of the cellular mechanisms leading to glaucomatous RGC degeneration and provide experimental data for future clinical trials of modulating the IL-17A signaling pathway as a target for neuroprotection.