The levels and significance of inflammasomes in the mouse retina following optic nerve crush

Abstract

Inflammasomes play an important role in neuroinflammation. However, their function during the secondary death of retinal cells after traumatic optic neuropathy and their dependence on pathogen stimuli remains unclear. Therefore, we evaluated the expression profiles of 10 different inflammasome-related mRNAs in the retina following an optic nerve crush (OPC) injury under both conventional sterile as well as non-sterile conditions, and validated two significantly varied ones on a protein level. While most factors were much more highly elevated in non-sterile conditions, both Nlrp1b and Nlrp3 inflammasome mRNAs were increased significantly on postoperative day 1 to day 7 in the mouse sterile OPC injury model. While production of the inflammation-associated cytokines IL-1β and IL-18 could be continuously detected on an mRNA level postoperatively, a clear peak could be seen on day 7 that coincided with maximal expression of caspase-1 mRNA and with observation of retinal ganglion cells death, despite the mice being held in specific-pathogen free conditions. As such, the pro-inflammatory cytokines activated by inflammasome activation during OPC injury may drive secondary cell death through pyroptosis, and inhibition of these delayed responses may be an important means of preventing worsened injury and loss of vision in trauma patients.