C1q dependency of retinal ganglion cell death in blast-mediated traumatic brain injury

Traumatic brain injury is a widespread health concern that annually affects millions of people worldwide, with blast-mediated TBI (bTBI) being of particular relevance to military personnel and civilians in war zones. Current treatments primarily target symptoms, rather than the underlying neuropathology, and are ultimately limited by the need for an improved etiological understanding of TBI. Here, we utilized a pre-clinical mouse model of bTBI, previously shown to evoke a high susceptibility to retinal ganglion cell (RGC) death, to investigate whether neuroinflammatory pathways associated with the complement factor 1q (C1q) complex contribute to RGC death. To test this, C57BL/6J (B6) mice with genetic knock-out of C1qa (B6.C1qa^ko) were exposed to bTBI, or sham control, with subsequent comparisons of RGC survival at durations of 5- and 16-weeks following exposure. Survival metrics consisted of quantifying RGC somas from immunostained retinal flat-mounts and axons from histochemically stained optic nerve cross sections. Relative to sham controls, no significant differences in the abundance of RGC somas in retina or axons in the optic nerve were detected in B6.C1qa^ko mice at either 5- or 16-weeks after bTBI exposure. These results demonstrate that loss of C1qa confers robust and persistent neuroprotection of RGCs and identify a C1q-dependent neuroinflammatory mechanism that contributes to pathways of neuronal death that are similar to other forms of neurodegeneration, particularly glaucoma.