Increased reactive astrocytes and NLRC4-mediated neuronal pyroptosis in advanced visual structures contralateral to the optic nerve crush eye in mice

Deling Li; Qinyuan Hu; Zongyi Zhan; Xinyi Zhang; Weiting Zeng; Liling Liu; Kaili Wu; Minbin Yu

doi:10.1016/j.exer.2025.110235

Increased reactive astrocytes and NLRC4-mediated neuronal pyroptosis in advanced visual structures contralateral to the optic nerve crush eye in mice

Exp Eye Res. 2025 Jan 9:110235. doi: 10.1016/j.exer.2025.110235. Online ahead of print.

Authors

Deling Li¹, Qinyuan Hu¹, Zongyi Zhan¹, Xinyi Zhang¹, Weiting Zeng¹, Liling Liu¹, Kaili Wu¹, Minbin Yu²

Affiliations

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic center, Sun Yat-sen University, Guangzhou 510000, Guangdong, China.
² State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic center, Sun Yat-sen University, Guangzhou 510000, Guangdong, China. Electronic address: yuminbin@mail.sysu.edu.cn.

PMID: 39798846
DOI: 10.1016/j.exer.2025.110235

Abstract

Currently, research on optic nerve injury predominantly focuses on the retina and optic nerve, but emerging evidence suggests that optic nerve injury also affects advanced visual structures like the superior colliculus (SC) and primary visual cortex (V1 region). However, the exact mechanisms have not been fully explored. This study aims to investigate the characteristics and mechanisms of pathology in the SC and V1 region after optic nerve crush (ONC) to deepen our understanding of the central mechanism of visual injury. After unilateral ONC, visual acuity in the injured eye declined, along with thinning of the retinal nerve fiber layer, and the latency and amplitude of FVEPs decreased. Furthermore, neuronal loss and degeneration were observed in the contralateral SC and V1 region, accompanied by astrocytic activation. Additionally, protein markers C3, and Serping1 for A1 astrocytes, which had neurotoxic effects and S100A10, and PTX3 for A2 astrocytes, which promoted tissue repair, were increased in the two regions. A1 astrocytes were mainly present in the early stages of observation, while A2 astrocytes were mainly increased later. Notably, NLRC4, GSDMD-N, cleaved caspase-1 expression, and IL-1β, IL-18 secretion increased in the contralateral SC and V1 region. Collectively, our findings reveal that A1 (neurotoxic) and A2 astrocytes (neuroprotective), NLRC4-mediated neuronal pyroptosis are enhanced in SC and V1 region contralateral to the ONC eye. The primary visual cortex responds to injury later than the superior colliculus after ONC, with less pronounced damage changes. Reactive astrocytes and NLRC4 inflammasome may act as promising targets for the prevention and treatment of optic nerve injury.

Keywords: NLRC4; optic nerve injury; primary visual cortex; pyroptosis; reactive astrocytes; superior colliculus.