Development of translational visual quality of life outcomes and non-invasive rehabilitation of visual loss

点击翻译按钮获取中文摘要

Traumatic brain injury (TBI) is a leading cause of injury among Veterans; an estimated 20% of recent Veterans have experienced some form of TBI. Veterans can also acquire non-service related TBIs, with over 2 million Americans having received some form of TBI. Many recent injuries have come via exposures to blast from improvised explosive devices. Blast explosions have affected service members from all American military engagements, even without overt or extensive blast exposure. Individuals exposed to TBI may experience ailments such as headache and learning deficits and may be at increased risk for long-term maladies such as neurodegenerative or psychiatric diseases Blast-mediated TBI has also caused visual dysfunction among affected individuals. Visual dysfunction produced by TBI includes changes in light sensitivity, ocular motility dysfunction, optic neuropathy and retinopathy, and homonymous visual field loss from cortical damage. Even with mild TBI, patients frequently report visual difficulties and a decreased visual quality of life that is not detected by routine eye exams. These symptoms likely represent subclinical disease in the eye and brain, which is underreported, and may progress to more severe visual deficits. While both visual and cognitive deficits manifest after blast exposure, the relationship between damage in the retina and the brain has not been described, and it is uncertain if visual damage after blast injury is a result of direct retinal injury, optic nerve injury, or retrograde degeneration due to neuron loss in visual processing centers of the brain. Establishing this relationship is critical to developing rehabilitative therapies in order to directly target the affected neurons. Furthermore, there has been difficulty modeling and testing the complexity of human vision and visual-cognitive relationships in laboratory models after blast exposure. This proposal addresses two needs that are impediments to improving Veterans’ quality of life through rehabilitation. The first is the lack of visual and visual-cognitive testing outcomes in pre-clinical rodent models that accurately reflect human visual processing. The outcomes of such animal models can also serve as translational indicators that disease states diminish the quality of life or that treatments can improve quality of life. Our proposal seeks to provide just such a pre-clinical rodent model. The second is lack of noninvasive, non-pharmacologic rehabilitation of visual function. Our proposal will address this gap by determining if transcranial direct current stimulation (tDCS) can leverage endogenous neuronal plasticity to rehabilitate visual function. Our central hypotheses are first that blast-mediated TBI results in synaptic dysregulation which can impair the ability of neurons to function efficiently. Second, we hypothesize that tDCS applied during visual rehabilitation therapy will lead to improved visual outcomes and thus improved visual-cognitive relationships and quality of life. We will analyze these using novel outcomes of vision and visual-cognitive relationships following TBI in a manner that reflects Veterans’ difficulties and quality of life – in addition to understanding how to rehabilitate this dysfunction.