近日，华中科技大学Fang Zheng团队发现，IL-33/ST2轴通过调节星形胶质细胞反应保护视网膜神经节细胞。2024年8月27日，《神经科学通报》杂志在线发表了这项成果。

研究人员报告了IL-33和ST2在小鼠视神经和视网膜中的高表达。删除IL-33或ST2会加重视网膜神经节细胞（RGC）的丧失、视网膜变薄和神经纤维退化。Il33^-/-小鼠中，视网膜神经退化与神经毒性星形胶质细胞的增加相关。

在体外实验中，重组IL-33（rIL-33）减轻了神经毒性星形胶质细胞的表型，并降低了促炎因子的表达，从而减轻了由神经毒性星形胶质细胞条件培养基引起的视网膜神经节细胞死亡。外源性IL-33处理改善了Il33^-/-和WT小鼠在视神经损伤后的RGC存活，但在ST2^-/-小鼠中未见改善。该研究强调了IL-33/ST2轴在调节反应性星形胶质细胞功能和在视神经损伤后提供RGC神经保护中的作用。

据介绍，IL-33及其受体ST2在组织修复和稳态中发挥重要作用。然而，它们在创伤性视神经病和青光眼中的作用仍不清楚。

附：英文原文

Title: The IL-33/ST2 Axis Protects Retinal Ganglion Cells by Modulating the Astrocyte Response After Optic Nerve Injury

Author: Qian, Zhigang, Jiao, Mengya, Zhang, Na, Tang, Xuhuan, Liu, Shiwang, Zhang, Feng, Wang, Chenchen, Zheng, Fang

Issue&Volume: 2024-08-27

Abstract: IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33-/- and WT mice after ON injury, but not in ST2-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.

DOI: 10.1007/s12264-024-01279-y

Source: https://link.springer.com/article/10.1007/s12264-024-01279-y