视神经外伤、青光眼等疾病导致的视神经损伤是造成患者视力下降甚至失明的原因。由于视神经损伤后不能再生，这类疾病往往会造成不可逆的视觉损害。虽然在哺乳动物眼内存在一些神经干细胞样的细胞，但视神经损伤后，这些细胞并不能发挥视网膜干细胞功能进行神经再生。我们前期研究显示，ephrin-A3/EphA4是视网膜神经干细胞的抑制因素，对其作用进行抑制，可能是保护视神经和视网膜神经节细胞，促进视神经再生的有效手段。本课题拟利用视神经损伤模型，研究ephrin-A3/EphA4在视神经和视网膜神经节细胞损伤过程中的作用，并尝试通过应用EphA4-Fc抑制EphA4的作用，激活视网膜内的神经干细胞，促进视网膜神经节细胞和视神经的再生，探讨视网膜神经干细胞再生的抑制因素及其作用机制，为视神经损伤和视网膜神经节细胞变性疾病的治疗提供新的思路。

Damage to optic nerve caused by various ocular disorders, including optic nerve trauma and glaucoma, is the main reason for vision loss and even blindness. The lack of neural regeneration in the visual system leads to irreversible visual deficits after traumatic optic nerve injuries. Although some neural stem-like cells reside in mammals’ eyes, they do not serve as retinal stem cells and regenerate retinal neurons after optic nerve damage. Previous research of our lab showed that ephrin-A3/EphA4 is a new potential inhibitory factor of intrinsic retinal stem cells. Inhibit the role of ephrin-A3/EphA4 could be an effective method for retinal ganglion cell protection and optic nerve regeneration. In the present study, we will use optic nerve crush animal model to clarify the role of ephrin-A3/EphA4 in retina and optic nerve after axonal injuries. We will analyze the regeneration of retinal ganglion cells and axons through intervention of EphA4 function by EphA4-Fc, the inhibitory factor of endogenous retinal stem cells, and further improve the strategy for retinal ganglion cell and optic nerve protection and regeneration.