IL-33 protects retinal structure and function via mTOR/S6 signaling pathway in optic nerve crush

• Published in: Experimental eye research Vol. 248; p. 110121
• Main Authors: Wang, Xinyue, Li, Jinmiao, Nie, Jiahe, Huang, Weifeng, Tang, Junjie, Peng, Yue, Gao, Yang, Lu, Rong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2024
• Subjects: Interlukin-33; Optic nerve crush model; Optic neuropathy; Optic nerve crush model; Optic neuropathy; Interlukin-33
• ISSN: 0014-4835; 1096-0007; 1096-0007
• DOI: 10.1016/j.exer.2024.110121

This study demonstrated the functions and molecular mechanisms of the IL-33/ST2 axis in experimental optic neuropathy. C57BL/6J mice were used to establish an optic nerve crush (ONC) model. ONC mice were administered with IL-33 intraperitoneal injection, with PBS vehicle as control. Immunofluorescence, quantitative RT-PCR, and western blot techniques were utilized to assess the expression of the IL-33/ST2 axis. The electroretinography (ERG), optical coherence tomography (OCT), H&E, and luxol fast blue were used to assess the structural and functional changes. Western blot was employed to detect the activation of the mTOR/S6 pathway. The IL-33 expression level in the inner nuclear layer of the retina in ONC mice reached its peak on day 3, accompanied by a significant increase in IL-33 receptor ST2 expression. IL-33 treatment promoted the survival of retinal ganglion cells, restored the thickness of inner retina layer (IRL), alleviated the demyelination of the optic nerve, and recovered the decreased amplitude of b-wave in ONC mice. Furthermore, administration of IL-33 activated the mTOR/S6 signaling pathway in RGCs, which was significantly suppressed in the ONC condition. This study indicated that boosting the IL-33/ST2/mTOR/S6 pathway can protect against structural and functional damage to the retina and optic nerve induced by ONC. As a result, the IL-33/ST2 axis holds potential as a therapeutic option for treating various optic neuropathies. •IL-33 and ST2 increased following optic nerve crush.•IL-33 treatment promoted the survival of retinal ganglion cells (RGCs).•IL-33 treatment restored the structure of the retina and the optic nerve, and recovered the decreased amplitude of b-wave in ONC mice.•IL-33 treatment activates mTOR/S6 pathway following optic nerve crush.