Liu Xiao, Duan Hongmei, Gao Limin, Yuan Linhao, Hao Peng, Zhao Wen, Gao Yudan, Huang Zitian, Wang Xi, Zhou Wenjianlong, Ma Shunchang, Wang Ningli, So Kwok-Fai, Yang Zhaoyang, Li Xiaoguang, Jia Wang
Department of Neurosurgery, Beijing Tiantan Hospital, National Center for Neurological Disorders, Capital Medical University, Beijing, 100070, China.
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
Sci China Life Sci. 2025 May 27. doi: 10.1007/s11427-024-2756-9.
Optic neuropathy is one of the main causes of irreversible blindness in the world, and there is no effective treatment in clinic. Both primary degeneration and secondary degeneration play an important role in the injury caused by optic neuropathy. Partial optic nerve transection (PONT) model can be used to study these two kinds of degeneration simultaneously. However, there is currently no measure that can effectively intervene in both types of injuries concurrently. Here, we constructed an expanded partial optic nerve transection (EPONT) model. Nerve growth factor (NGF)-chitosan locally implanted into the injured area could simultaneously intervene in the secondary and primary degeneration, not only protecting the ventral part of the injured optic nerve, but also promoting the regeneration of the dorsal part. Visual functions, including pupillary light reflex and depth perception, were also well preserved. NGF-chitosan exerted biological effects by enhancing the expression of NGF and tyrosine kinase A (TrkA) in the optic nerve and retinal ganglion cells (RGCs). Furthermore, NGF-chitosan played a protective and repairing role by inhibiting the activation of microglia in the ventral area of the injured optic nerve and increasing the expression of mammalian target of rapamycin (mTOR) in RGCs. Our results demonstrate that the local use of NGF-chitosan in the injured area effectively repaired the optic nerve, which provides a new measure for the clinical treatment of optic nerve injury.
视神经病变是全球不可逆性失明的主要原因之一，临床上尚无有效治疗方法。原发性变性和继发性变性在视神经病变所致损伤中均起重要作用。部分视神经横断（PONT）模型可用于同时研究这两种变性。然而，目前尚无措施能同时有效干预这两种损伤。在此，我们构建了一种扩展的部分视神经横断（EPONT）模型。将神经生长因子（NGF）-壳聚糖局部植入损伤区域可同时干预继发性和原发性变性，不仅能保护损伤视神经的腹侧部分，还能促进背侧部分的再生。包括瞳孔对光反射和深度感知在内的视觉功能也得到了良好保留。NGF-壳聚糖通过增强视神经和视网膜神经节细胞（RGCs）中NGF和酪氨酸激酶A（TrkA）的表达发挥生物学效应。此外，NGF-壳聚糖通过抑制损伤视神经腹侧区域小胶质细胞的激活以及增加RGCs中雷帕霉素靶蛋白（mTOR）的表达发挥保护和修复作用。我们的结果表明，在损伤区域局部使用NGF-壳聚糖可有效修复视神经，为视神经损伤的临床治疗提供了一种新措施。
