Novel Combinatorial Approaches to Repair Visual System After Optic Nerve Damage
Abstract
Vision, the ability to see, is perhaps one of the most important senses in our lives, as it is critical for navigation and survival. Military Service members are more likely than non-military civilians to encounter traumatic events that can result in brain injury. Traumatic brain injury (TBI) is a debilitating, multifaceted trauma that frequently occurs in the military patient population. One of the facets of TBI is damage to the optic nerve, which can result in significant visual impairment. About 75% of active military personnel subjected to trauma suffer from progressive glaucoma or optic nerve injury (also known as optic neuropathy). The optic nerve works like a highway, connecting the eye to the brain. When it is damaged, such as what often occurs in TBI, the eye no longer can send visual information to the brain, resulting in irreversible blindness. Currently, there is no treatment available to patients that can regenerate the damaged optic nerve needed to reverse blindness. There has been some progress in animal research aimed at finding a cure for repairing the damaged optic nerve. One promising and relatively safe method is hypothermia exposure (cooling of the body) with beneficial effects observed in preclinical animal models to reduce the rate of nerve damage. Another therapeutic approach is the use of gene therapy to provide nerve protection and permit regeneration. However, these approaches, when given individually, have limited therapeutic effects. An optimized approach would be to combine the individual treatments together, ultimately leading to additive and synergistic effects. Such combinatorial approaches have never been tested in animal models of TBI-induced optic nerve injury. Our proposed study will explore this exciting possibility. The main objective of this study is to determine whether our unique combinatorial strategies rescue cells and promote optic nerve regeneration with a greater efficacy in clinically relevant models of optic nerve injury. To this end, we will use cutting-edge tissue imaging techniques, genetically modified mice, and innovative gene therapy approaches. Specific Aims: Aim 1. To determine where and when the optic nerve is damaged after head trauma in preclinical animal models of TBI. There is a pressing need to better characterize damage to the optic nerve in animal models of injury due to a limited number of animal studies available. Mice are readily available as gene knockout mice and provide an excellent model to study genes and diseases and to develop potential therapeutics. Aim 2. To examine whether a combinatorial treatment paradigm, consisting of hypothermia and gene therapy, can work synergistically to protect the eyes and optic nerve more efficiently than individual treatments alone. Aim 3. To examine the effects of combinatorial gene therapy in promoting optic nerve regeneration and restoration of lost vision after optic nerve injury in animals. Impact: There is currently no treatment available to restore vision after optic nerve injury. Hypothermia and gene therapy are viable therapeutic options. Combined effects of these strategies have not been examined before in treating this complex vision problem. The potentially robust cell protection and regeneration conferred by these therapeutic strategies will exert a significant impact in the field of neuroscience and on treatment of patients with nerve injury. Military Relevance: Military personnel are at greater risk of incurring optic nerve injury. This proposal will investigate combinatorial therapeutic interventions to rescue dying neurons, promote regeneration, and restore vision, with the added potential to be administered in the clinic and on the battlefield. Overall Impact: Our study could prove to be significant to the field of neuroscience, vision research, and in the clinical setting for a number of reasons. First, hypothermia is considered relatively safe in humans. Second, while the saf
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910736
Entities
People
- Kevin Park
Organizations
- United States Army
- University of Miami