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

创伤性脑损伤(TBI)是退伍军人受伤的主要原因；据估计，最近退伍军人中有20% 都经历过某种形式的脑损伤。退伍军人还可以获得非服役相关的TBI，超过200万 接受过某种形式的脑损伤的美国人。最近的许多伤害都是由于暴露于爆炸造成的 简易爆炸装置。爆炸影响了所有美国军队的服役人员 参与，即使没有公开或广泛的爆炸暴露。暴露于脑损伤的个人可能会经历 头痛和学习障碍等疾病，并可能增加患长期疾病的风险，如 神经退行性疾病或精神疾病由冲击波介导的脑外伤也导致了 受影响的个体。颅脑损伤引起的视觉功能障碍包括光敏感度、眼球运动能力的改变 功能障碍、视神经病变和视网膜病变，以及皮质损伤所致的同名视野丧失。连 对于轻度脑外伤，患者经常报告视力困难和视觉生活质量下降 通过常规眼科检查发现。这些症状可能代表着眼睛和大脑的亚临床疾病， 这一点被低估了，并可能进展为更严重的视力缺陷。虽然视觉和认知都是如此 在冲击波暴露后出现缺陷，视网膜和大脑的损害之间的关系还没有 冲击伤后的视力损害是否由直接的视网膜损伤、视神经损伤所致尚不确定。 神经损伤，或由于大脑视觉处理中心的神经元丢失而导致的退行性变性。 建立这种关系对于发展康复治疗至关重要，以便直接针对 受影响的神经元。此外，对人类视觉的复杂性进行建模和测试一直存在困难 以及爆炸暴露后实验室模型的视觉-认知关系。 这项建议解决了两个阻碍退伍军人提高生活质量的需求 康复。第一个是缺乏临床前啮齿动物模型的视觉和视觉认知测试结果。 准确地反映了人类的视觉处理。这种动物模型的结果也可以作为 疾病状态降低生活质量或治疗可以提高生活质量的翻译指标 生活。我们的建议就是为了提供这样一种临床前啮齿动物模型。第二个是缺乏非侵入性， 视功能的非药物康复。我们的提案将通过确定 经颅直流电刺激可以利用内源性神经元的可塑性来恢复视力 功能。 我们的中心假设是，首先，BLAST介导的脑损伤导致突触调节失调，这可能会损害 神经元有效运作的能力。第二，我们假设tdcs在视力康复过程中的应用。 治疗将导致改善视觉结果，从而改善视觉-认知关系和质量 生活。我们将使用脑外伤后视觉和视觉-认知关系的新结果来分析这些因素 反映退伍军人的困难和生活质量的方式-除了了解如何康复 这种功能障碍。

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.