Neuritin (Nrn1) is a small highly conserved extracellular membrane protein involved in the process of neural cell survival and differentiation, axonal and dendritic growth, and synapse formation and maturation. Previous studies have demonstrated that intravitreal injection of recombinant Nrn1 as a gene therapy could alleviate retinal ganglion cell (RGC) apoptosis and promote optic nerve axon regeneration after optic nerve crush (ONC). However, the mechanism underlying the repairing effect of Nrn1 against optic never injury remains elusive. In this study, a rAAV2-mediated Nrn1 overexpression vector (AAV2-Nrn1) was applied to treat ONC through intravitreal injection for the purpose of further exploring the effect and mechanism of Nrn1 in repairing the injured optic nerve. The results showed that AAV2-Nrn1 was mainly transfected into RGCs without affecting astrocytes. Nrn1 overexpression effectively reduced RGC apoptosis and promoted optic nerve regeneration and visual function restoration as demonstrated by retinal imaging, histopathological analysis, and physiological function detection in vivo following ONC. Immunoblot assay revealed that functional molecules of Nrn1 activated the Akt1 and Stat3 pathways and inhibited the mitochondrial apoptotic pathway. The results of the present study may provide experimental evidence for further application of Nrn1 to the clinical treatment of optic nerve injury.

Neuritin (Nrn1) 是一种小的高度保守的细胞外膜蛋白，参与神经细胞存活和分化、轴突和树突生长以及突触形成和成熟的过程。先前的研究表明，玻璃体内注射重组 Nrn1 作为基因治疗可以减轻视网膜神经节细胞 (RGC) 凋亡并促进视神经挤压 (ONC) 后视神经轴突再生。然而，Nrn1 对视神经损伤的修复作用的潜在机制仍然难以捉摸。本研究采用rAAV2介导的Nrn1过表达载体（AAV2-Nrn1）通过玻璃体内注射治疗ONC，以进一步探索Nrn1修复损伤视神经的作用和机制。结果表明，AAV2-Nrn1主要转染到RGC中，不影响星形胶质细胞。Nrn1 过表达有效地减少了 RGC 细胞凋亡并促进了视神经再生和视觉功能恢复，如 ONC 后视网膜成像、组织病理学分析和体内生理功能检测所证明的。免疫印迹分析显示 Nrn1 的功能分子激活 Akt1 和 Stat3 通路并抑制线粒体凋亡通路。本研究结果可为Nrn1进一步应用于视神经损伤的临床治疗提供实验依据。ONC后的体内生理功能检测。免疫印迹分析显示 Nrn1 的功能分子激活 Akt1 和 Stat3 通路并抑制线粒体凋亡通路。本研究结果可为Nrn1进一步应用于视神经损伤的临床治疗提供实验依据。ONC后的体内生理功能检测。免疫印迹分析显示 Nrn1 的功能分子激活 Akt1 和 Stat3 通路并抑制线粒体凋亡通路。本研究结果可为Nrn1进一步应用于视神经损伤的临床治疗提供实验依据。