# Mitochondria: controllers of trauma-induced secondary neurodegeneration onset

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $477,794

## Abstract

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.

## Key facts

- **NIH application ID:** 10905349
- **Project number:** 1R01EY036252-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** TONIA S REX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $477,794
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905349

## Citation

> US National Institutes of Health, RePORTER application 10905349, Mitochondria: controllers of trauma-induced secondary neurodegeneration onset (1R01EY036252-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10905349. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*