Novel Combinatorial Approaches to Repair Visual System after Optic Nerve Damage
Technical Report,01 Sep 2019,31 Aug 2020
University of Miami Miller School of Medicine Miami United States
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Background The neurons in the eye called retinal ganglion cells RGCs send visual information through nerve fibers that travel into the optic nerve to reach the brain. Damage to the optic nerve resulting from traumatic brain injury TBI and traumatic optic neuropathy TON can result in the death of these neurons, and subsequent visual impairment. There is no treatment available to restore vision once the damage is done. We have previously discovered specific genes that induce robust optic nerve regeneration in mice. Additionally, we have demonstrated that genetic modification of cell death-related genes render RGCs highly resistant to injury. ObjectiveHypothesis The objective of this proposal is to determine the ability of combinatorial strategies to rescue RGCs and improve optic nerve regeneration in clinically-relevant models of optic nerve injury. The hypotheses of our study are i using a combinatorial treatment strategy comprised of hypothermia exposureand neuroprotective gene therapy will further improve RGC survival after TBI, and ii regenerative gene therapy will promote optic nerve regeneration and restoration of lost vision after clinically-relevant optic nerve injury generated close to the brain. The specific aims are Aim 1. Systematically characterize the site, type, and time course of damage in the visual pathway, and long term subtype-specific RGC loss following TBI. Currently, there are gaps in the knowledge of the type and extent of axonal damage that occurs in the optic pathway after TBI. Therefore, more comprehensive animal studies are needed to better understand the pathophysiology of optic nerve damage and visual impairment after TBI. Aim 2. Assess the individual and combined effects of hypothermia and gene therapy in preventing RGC death after TBI.
- Anatomy and Physiology
- Genetic Engineering and Molecular Biology