NLRP3 Deficiency Attenuates Secondary Degeneration of Visual Cortical Neurons Following Optic Nerve Injury
- 52 Downloads
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.
KeywordsNLRP3 Visual cortex Optic nerve injury Visual cortical degeneration
We would like to thank Prof. Yuan-Guo Zhou from the Army Medical Center of the People’s Liberation Army and Prof. Feng Mei from the Army Medical University (AMU) for project consultation and data evaluation, and thank Prof. Bo Peng from Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, for technical support. This work was supported by the National Natural Science Foundation of China (81570840 and 81200926), the Academician-Led Science and Technological Innovation of Chongqing (cstc2017jcyj-yszxX0006), and the Research Foundation of the Department of Ophthalmology in Daping Hospital, AMU (9-2543).
Conflict of interest
The authors claim that there are no conflicts of interest.
- 32.Leamey CA PD, Dreher B. Comparative survey of the mammalian visual system with reference to the mouse. In: Chalupa,Williams RW (Eds). Eye, Retina, and Visual System of the Mouse. MIT Press, 2008: 35–60.Google Scholar
- 33.Cusack CL, Swahari V, Hampton Henley W, Michael Ramsey J, Deshmukh M. Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning. Nat Commun 2013, 4: 1876.Google Scholar
- 54.Kaushal V, Dye R, Pakavathkumar P, Foveau B, Flores J, Hyman B, et al. Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ 2015, 22: 1676–1686.PubMedPubMedCentralCrossRefGoogle Scholar