Zhang Ruixue, Xie Yunxiao, Zhang Miao, Li Zhiheng, Guo Lijie, Wei Huixia, Li Xiaomeng, Xin Jizhao, Yang Zhaohui, Wen Ying, Hao Jiawen, Li Xianglin, Yin Xuewei, Jiang Wenjun, Bi Hongsheng, Guo Dadong
Shandong University of Traditional Chinese Medicine, Jinan, China.
Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Exp Mol Med. 2025 Jul 3. doi: 10.1038/s12276-025-01489-y.
Myopia is a serious public health issue worldwide. Damage to retinal ganglion cells (RGCs) in the retina induces degeneration of the visual cortex, which is known as anterograde trans-synaptic degeneration (TSD). However, the role of TSD in myopia is still unknown. Here single-cell RNA-sequencing revealed the activation of RGC apoptotic signals in the retinal ganglion and the remodeling of synapses in the visual cortex in myopia. The thickness of the retinal nerve fiber layer was negatively correlated with the degree of damage to the visual cortex and damage to neurons in the visual pathway and to the synaptic structure and function of the visual cortex indicated the occurrence of anterograde TSD in the visual pathway. The knockdown of Fos, which inhibited retinal neuronal apoptosis, suppressed TSD, indicating that myopia can aggravate RGC apoptosis, induce anterograde TSD and thus aggravate synaptic remodeling. Our findings provide a new experimental basis for understanding the pathogenesis of myopia.
近视是一个全球性的严重公共卫生问题。视网膜中视网膜神经节细胞（RGCs）的损伤会导致视觉皮层退化，这被称为顺行性跨突触变性（TSD）。然而，TSD在近视中的作用仍然未知。在这里，单细胞RNA测序揭示了近视时视网膜神经节中RGC凋亡信号的激活以及视觉皮层中突触的重塑。视网膜神经纤维层的厚度与视觉皮层的损伤程度呈负相关，视觉通路中神经元的损伤以及视觉皮层的突触结构和功能的损伤表明视觉通路中发生了顺行性TSD。抑制视网膜神经元凋亡的Fos基因敲低抑制了TSD，表明近视可加重RGC凋亡，诱导顺行性TSD，从而加重突触重塑。我们的研究结果为理解近视的发病机制提供了新的实验依据。
