“Brn3C-STXBP1-Stx1a”通路促进视神经损伤后的修复再生及调控机制

视神经损伤是青光眼进程的重要组成部分，高眼压损伤后视觉保护仅针对死亡的RGCs展开时，可能由于忽略对视神经的保护而使受损的视功能恢复不佳。我们通过鼠类青光眼模型及视神经损伤模型发现，转录因子Brn3C、囊泡融合蛋白结合蛋白STXBP1和囊泡融合蛋白Stx1a在损伤后降低，进一步通过果蝇神经元轴突损伤模型发现Brn3C、STXBP1和Stx1a具有促进Class Ⅲ和Ⅳ型神经元轴突损伤后再生的能力，由于Brn3C、STXBP1和Stx1a在进化中高度保守，我们推测：视神经损伤后，具有促轴突再生能力的Brn3C、STXBP1和Stx1a表达降低，进而引起损伤后的视神经再生能力低下，即“Brn3C-STXBP1-Stx1a”具有促进损伤后视神经再生的功能。本研究结果将为青光眼损伤后视神经的再生修复机制提供最新认识，为挽救青光眼后损害视功能及探索相关药物干预靶点方提供前期理论和实验依据。

Optic nerve injury plays an important role in the process of glaucoma. The lack of consideration of optic nerve protection in the rescue strategy may be partly responsible for the limited visual function recovery with the types of protective methods for retinal neurons in glaucoma injury. In our preliminary data, we found that the expression of the transcription factor Brn3C, Syntaxin-1A (Stx1a) and Syntaxin Binding Protein 1 (STXBP1) are decreased in mouse experimental glaucoma injury model and optic nerve crush model. Further, we found that the three high conserved genes, Brn3C, STXBP1 and Stx1a, have the ability to promote axon regeneration in Drosophila Class Ⅲ and Ⅳ dendritic arbor neurons after axon injury. Taken together, these results suggest that the decreased Brn3C, STXBP1 and Stx1a expression, induced by optic nerve injury, may lead to limited regeneration ability of optic nerve. In other words, it is that "Brn3C-STXBP1-Stx1a" pathway could promote optic nerve regeneration after injury. The research on the molecular mechanism of Brn3C-STXBP1-Stx1a pathway may provide new insight in developing therapeutic strategies to uncover the mystery of optic nerve regeneration and alleviate the visual loss in glaucoma.