BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage

In this study,Bax+/ − mice were used to test the hypothesis that lowering the quantity of BAX in RGCs would delay apoptosis following optic nerve injury. RGCs were damaged by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN, and quantitative PCR were used to monitor the status of the BAX activation mechanism in the months following injury. The apoptotic susceptibility of injured cells was directly tested by virally introducing GFP-BAX intoBax−/− RGCs after injury. The competency of quiescent RGCs to reactivate their BAX activation mechanism was tested by intravitreal injection of the JNK pathway agonist, anisomycin. Twenty-four weeks after ONC,Bax+/ − mice had significantly less cell loss in their RGC layer thanBax+/+ mice 3  weeks after ONC.Bax+/ − andBax+/+ RGCs exhibited similar patterns of nuclear phospho-cJUN accumulation immediately after ONC, which persisted inBax+/ − RGCs for up to 7  weeks before abating. The transcriptional activation of BAX-activating genes was similar inBax+/ − andBax+/+ RGCs following ONC. Intriguingly, cells deactivated their BAX activation mechanism between 7 and 12  weeks after crush. Introduction of GFP-BAX intoBax−/− cells at 4  weeks after ONC showed that these cells had a nearly normal capacity to activate this protein, but this capacity was lost 8 weeks after crush. Collectively, these data suggest that 8–12 weeks after crush, damaged cells no longer displayed increased susceptibility t...

Source: Molecular Neurobiology - January 31, 2020 Category: Neurology Source Type: research