NLRP3 Deficiency Attenuates Secondary Degeneration of Visual Cortical Neurons Following Optic Nerve Injury.

Abstract

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.