Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy
Abstract
Over 186,000 eye injuries were diagnosed in fixed (not deployed) U.S. Military medical facilities from 2000-2011. In addition, approximately half of Veterans with blast-induced mild traumatic brain injury (TBI) have damage to the visual system, much of which is not detected until months after injury. These injuries were recently projected to cost the U.S. economy $25 billion in healthcare, work lost, and family support. In addition, each year approximately 50,000 U.S. citizens experience permanent vision loss as a result of trauma. There are no known effective therapies to block or restore vision loss after trauma to the visual system, so success in this project would be a very important breakthrough for these patients. The objective of this study is to identify treatments for degeneration and vision loss secondary to trauma that can be quickly translated to the clinic. We have developed a clinically relevant model of blast trauma that replicates the same types of damage detected in injured Service members including delayed vision loss and optic nerve degeneration (i.e., traumatic optic neuropathy). Further, our results suggest that the degeneration that occurs to the visual system after blast is similar what occurs in TBI and spinal cord injury. Therefore, successful protection of neurons in this study may have broader implications. In Specific Aim 1, we will further explore the underlying cause of neuron death and vision loss after trauma with the hope of identifying new therapeutic targets. In Specific Aims 2 and 3, we will test the efficacy of two neuroprotective agents, which were chosen based on their known mechanisms of action, Food and Drug Administration (FDA) approval, and our knowledge of the molecular processes that are enacted early after blast in our model, prior to the onset of axon degeneration. In Specific Aim 2, we will test the ability of galantamine to restore neuronal signaling, vision, and optic nerve health. Galantamine is an FDA-approved drug for the treatment of Alzheimer s disease. In Specific Aim 3, we will test the ability of erythropoietin (EPO) to preserve a healthy environment in the retina after trauma. EPO is currently in Phase III clinical trials for the treatment of TBI. In both Specific Aims 2 and 3, we will assess efficacy by quantifying vision and optic nerve structure. Preservation of vision in our model will be a strong rationale for testing the therapeutics in patients with vision loss from either an explosive device (i.e., Service members and Veterans) or from blunt force trauma (i.e., Service members, Veterans, and family members). Both of the proposed neuroprotective agents are already used in the clinic for other applications and have good safety profiles, which should make translation back to the clinic straightforward with a low risk-to-benefit ratio. Initiation of a clinical study based on our findings would occur in collaboration with (1) our commercial partner, Nanoferix; (2) Dr. Marcus Colyer, a vitreoretinal surgeon at Walter Reed National Military Medical Center; and (3) faculty in the Vanderbilt Eye Institute, which houses several clinicians who specialize in ocular trauma, including our Chair, Dr. Sternberg and serves (a) Vanderbilt University Hospital, the region s only Level 1 trauma facility and (b) the Tennessee Valley Health Care Veterans Administration Hospital. In summary, the proposed project has the potential to benefit Service members, Veterans, and their family by identifying therapeutic options for blocking neuron death and vision loss after trauma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510559
Entities
People
- Tonia Rex
Organizations
- United States Army
- Vanderbilt University