Each year approximately 3 million United States citizens incur traumatic brain injury (TBI). An additional 50,000 United States citizens derive permanent vision loss from direct ocular trauma. Both brain and ocular trauma can involve the optic nerve causing traumatic optic neuropathy (TON) even in the absence of physical damage, i.e. indirect (ITON). ITON occurs in 2-5% of TBI civilian patients. Currently there are no effective treatments available for ITON. Secondary axon degeneration and resulting vision loss occurs 3-6 weeks post-injury in ITON patients. Similarly, in our mouse model of ITON, there is immediate loss of axons followed by a second wave of axon degeneration at 14 days post-injury. This gap between initial insult and secondary degeneration represents a window of therapeutic opportunity. In our model, initiation of secondary degeneration coincides with an increase in the mitochondrial oxygen free radical, superoxide and a decrease in the scavenger, superoxide dismutase 2 (SOD2). Further, treatment with vitamin E prevents these changes and promotes RGC axon survival and preservation of vision. These data support a role for dysfunctional mitochondria in secondary axon degeneration. In other optic neuropathy models, astrocytes promote RGC axon function through transfer of healthy mitochondria, while delivery of metabolic resources prolongs axon survival. Based on these results, we propose that the timing of secondary axon degeneration after ITON is controlled by astrocyte support of the ratio of normal to dysfunctional mitochondria in surviving axons. As a corollary to this hypothesis, we also propose that exogenous mitochondrial transplantation will delay onset of secondary degeneration. We will test this through the following Specific Aims: 1) Quantify mitochondria dysfunction following ITON; 2) Quantify resource sharing from astrocytes to surviving RGC axons prior to onset of secondary neurodegeneration after ITON; 3) Quantify mitochondrial dysfunction immediately prior to and during ITON-induced secondary neurodegeneration. Upon successful completion of these studies we will know how mitochondria and mitochondrial quality control processes determine the timing of onset of secondary neurodegeneration after ITON. This insight will allow us, in future studies, to test novel therapies that could further slow, prevent, or decrease secondary neurodegeneration after ITON.