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

转化视觉生活质量结果的发展和视力丧失的非侵入性康复

• 批准号: 10597512
• 负责人: Matthew M. Harper
• 金额: --
• 依托单位: IOWA CITY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597512
• 关键词: Accidents; Address; Affect; American; Animal Model; Biological Assay; Blast Injuries; Blindness; Brain; Cognitive; Cognitive deficits; Development; Devices; Disease; Explosion; Exposure to; Eye; Functional disorder; Goals; Headache; Human; Impairment; Individual; Injury; Laboratories; Learning; Location; Mediating; Mental disorders; Military Personnel; Modeling; Neuraxis; Neurodegenerative Disorders; Neuronal Plasticity; Neurons; Ophthalmic examination and evaluation; Optic Nerve Injuries; Outcome; Patients; Pharmacology; Photic Stimulation; Photophobia; Preclinical Testing; Quality of life; Rattus; Rehabilitation therapy; Reporting; Retina; Retinal Diseases; Retrograde Degeneration; Risk; Rodent Model; Supportive care; Symptoms; Synapses; Synaptic plasticity; TBI treatment; Terrorism; Testing; Tissues; Traumatic Brain Injury; Veterans; Vision; Visual; Visual Fields; Workplace; blast exposure; cell motility; cognitive testing; combat; experience; improved; mild traumatic brain injury; neuron loss; novel; optic nerve disorder; pre-clinical; response; service member; vision rehabilitation; visual dysfunction; visual processing

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.

创伤性脑损伤（TBI）是退伍军人受伤的主要原因。估计有20％的最近退伍军人 经历了某种形式的TBI。退伍军人还可以收购非服务相关的TBI，超过200万 美国人收到了某种形式的TBI。最近的许多伤害是通过暴露来爆炸的 简易的爆炸装置。爆炸爆炸影响了所有美国军方的服务成员 即使没有明显或广泛的爆炸暴露，也可以参与。接触TBI的个人可能会经历 标题和学习缺陷等疾病，可能会增加长期疾病的风险 神经退行性或精神病性疾病爆炸介导的TBI也引起了视觉功能障碍 受影响的人。 TBI产生的视觉功能障碍包括光灵敏度的变化，眼运动性 功能障碍，视神经病变和视网膜病变以及皮质损伤的同型视野损失。甚至 使用温和的TBI，患者经常报告视觉困难和视觉质量降低，而不是 通过常规眼检查检测。这些符号可能代表眼睛和大脑中的亚临床疾病， 虽然视觉和认知都被低估了，并且可能会发展为更严重的视觉缺陷。 缺陷在爆炸暴露后表现出来，视网膜和大脑的损害之间的关系尚未 被描述了，尚不确定爆炸损伤后视觉损害是否是直接残留损伤的结果 神经损伤或由于大脑视觉处理中心的神经元丧失而导致的逆行变性。 建立这种关系对于开发康复疗法至关重要，以直接针对 受影响的神经元。此外，很难建模和测试人类视力的复杂性 爆炸暴露后实验室模型中的视觉认知关系。 该提议解决了两种需求，这些需求是通过 康复。首先是临床前啮齿动物模型中缺乏视觉和视觉认知测试结果 这准确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方法的转化指标可以提高质量 生活。我们的建议旨在提供这样的临床前啮齿动物模型。第二个是缺乏无创的， 视觉功能的非药物康复。我们的建议将通过确定是否是否 经颅直流刺激（TDC）可以利用内源性神经元可塑性来恢复视觉 功能。 我们的中心假设首先是爆炸介导的TBI导致突触失调，这可能会损害 神经元有效发挥功能的能力。其次，我们假设在视觉康复期间使用TDCS 疗法将改善视觉结果，从而改善视觉认知关系和质量 生活。我们将使用TBI之后的视觉和视觉认知关系的新结果来分析这些 反映退伍军人的难度和生活质量的方式 - 除了了解如何康复 这种功能障碍。