In
glaucoma, harmful intraocular pressure often contributes to retinal ganglion cell death. It is not clear, however, if intraocular pressure directly insults the retinal ganglion cell axon, the
soma, or both. The pathways that mediate pressure-induced retinal ganglion cell death are poorly defined, and no molecules are known to be required. DBA/2J mice deficient in the proapoptotic molecule
BCL2-associated X protein (BAX) were used to investigate the roles of BAX-mediated cell death pathways in
glaucoma. Both Bax+/- and Bax-/- mice were protected from retinal ganglion cell death. In contrast, axonal degeneration was not prevented in either Bax+/- or Bax-/- mice. While BAX deficiency did not prevent axonal degeneration, it did slow axonal loss. Additionally, we compared the effects of BAX deficiency on the
glaucoma to its effects on retinal ganglion cell death due to two insults that are proposed to participate in
glaucoma. As in the
glaucoma, BAX deficiency protected retinal ganglion cells after axon injury by optic nerve crush. However, it did not protect retinal ganglion cells from
N-methyl-D-aspartate (
NMDA)-induced excitotoxicity. BAX is required for retinal ganglion cell death in an inherited
glaucoma; however, it is not required for retinal ganglion cell axon degeneration. This indicates that distinct somal and axonal degeneration pathways are active in this
glaucoma. Finally, our data support a role for
optic nerve injury but not for
NMDA receptor-mediated excitotoxicity in this
glaucoma. These findings indicate a need to understand axon-specific degeneration pathways in
glaucoma, and they suggest that distinct somal and axonal degeneration pathways may need to be targeted to save vision.