CircRNA176/miR-21调控星形胶质细胞活化影响视神经损伤后轴突再生的机制研究

视神经损伤后轴突再生修复困难，最终导致不可逆的视觉功能障碍甚至失明，严重影响患者身心健康。星形胶质细胞的过度活化是引起视神经损伤后轴突再生障碍的重要因素。前期研究已证实miR-21通过调节EGFR信号通路调控星形胶质细胞活化。近期我们发现circRNA176可抑制星形胶质细胞活化。然而circRNA176对星形胶质细胞活化的调控机制尚不清楚。前期研究我们进一步发现circRNA176可与miR-21结合。我们推测circRNA176可能通过海绵吸附miR-21，影响下游EGFR信号通路进而抑制星形胶质细胞活化。本项目运用细胞和分子生物学、视神经损伤动物模型、显微注射技术及电生理技术等研究方法，在申请人前期研究的基础上，围绕视神经损伤后神经再生这一核心问题，阐明circRNA176调控星形胶质细胞活化的分子机制，为探索视神经损伤后再生修复提供理论依据。

It is difficult to regenerate and repair axons after optic nerve injury, which eventually leads to irreversible visual dysfunction and even blindness, which seriously affects the physical and mental health of patients. The overactivation of astrocytes is an important factor in optic nerve regeneration. Previous studies have confirmed that the epigenetic modified molecule miR-21 regulates the activation of astrocytes through the EGFR pathway. Recently, circRNA176 was found to inhibit the activation of astrocytes. However, the regulatory mechanism of circRNA176 on the activation of astrocytes remains unclear. It was further found that circRNA176 could bind to miR-21.We hypothesized that circRNA176 may adsorb miR-21 through sponge, affecting downstream EGFR signaling pathway and thereby inhibiting the activation of astrocytes. The research methods of cell and molecular biology, animal model of optic nerve injury, microinjection technology and electrophysiological technology are applied in this project. Based on the applicant's previous research, the molecular mechanism of circRNA176 regulating the activation of astrocytes was clarified around the core issue of nerve regeneration after optic nerve injury, so as to provide a theoretical basis for exploring the regeneration of optic nerve injury.