Abstract
Purpose :
This study was aimed at investigating the protective roles and molecular mechanisms of the IL-33/ST2 axis in experimental optic neuropathy.
Methods :
An optic nerve crush (ONC) model was established in 8-week-old C57BL/6J mice. ONC mice were treated with IL-33 intraperitoneal injection, with PBS vehicle (sham) as control. The expression of IL-33/ST2 axis was examined using immunofluorescence, quantitative RT-PCR, and western blotting. Electroretinography (ERG), optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and luxol fast blue (LFB) staining were used to assess the structural and functional changes in the retina and optic nerve. The ST2/mTOR/S6 signaling pathway was detected through western blotting.
Results :
The IL-33 expression level was observed to reach the peak at day 3 in the inner nuclear layer (INL) of ONC mice. IL-33 receptor ST2 expression increased significantly at day 7. IL-33 treatment promoted the survival of retinal ganglion cells (RGCs), restored the thickness of inner retinal layer (IRL), alleviated the demyelination of the optic nerve, and recovered the decreased amplitude of b-wave in ONC mice. Furthermore, IL-33 administration activated the mTOR/S6 signaling pathway, which was significantly suppressed in the ONC condition.
Conclusions :
Our findings demonstrate that boosting the IL-33/ST2/mTOR/S6 signaling pathway can protect the retina and optic nerve from structural and functional damage caused by ONC. Consequently, the IL-33/ST2 axis shows promise as a potential therapy for various optic neuropathies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.