NLRP3 Deficiency Attenuates Secondary Degeneration of Visual Cortical Neurons Following Optic Nerve Injury
Zhou Zhang1 • Wenyi Liu1 • Yubin Huang2 • Linlin Luo1 • Xiaofeng Cai1 • Yunjia Liu1 • Liqianyu Ai1 • Jun Yan3 • Sen Lin1 • Jian Ye 1
1 Department of Ophthalmology, Research Institute of Surgery and Daping Hospital, Army Medical Center of the People’s Liberation Army (PLA), Army Medical University, Chongqing 400042, China
2 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, China
3 Department 1, Research Institute of Surgery and Daping Hospital, Army Medical Center of the PLA, Army Medical University, Chongqing 400042, China
In the visual pathway, optic nerve (ON) injury may cause secondary degeneration of neurons in distal regions, such as the visual cortex. However, the role of the neuroinflammatory response in regulating secondary impairment in the visual cortex after ON injury remains unclear. The NOD-like receptor family pyrin domain containing 3 (NLRP3) is an important regulator of neuroinflammation. In this study, we established a mouse model of unilateral ON crush (ONC) and showed that the expression of NLRP3 was significantly increased in the primary visual cortex (V1) as a response to ONC and that the NLRP3 inflammasome was activated in the contralateral V1 1 days–14 days after ONC. Ablation of the NLRP3 gene significantly decreased the trans-neuronal degeneration within 14 days. Visual electrophysiological function was improved in NLRP3−/− mice. Taken together, these findings suggest that NLRP3 is a potential therapeutic target for protecting visual cortical neurons against degeneration after ON injury.
NLRP3; Visual cortex; Optic nerve injury; Visual cortical degeneration