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: 10015503
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015503
• 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; cell motility; cognitive testing; combat; experience; improved; member; mild traumatic brain injury; neuron loss; novel; optic nerve disorder; pre-clinical; response; service member; vision rehabilitation; 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% 的新退伍军人 经历过某种形式的 TBI。退伍军人还可以获得与服役无关的 TBI，超过 200 万 美国人曾遭受过某种形式的创伤性脑损伤。最近许多受伤都是由于暴露在爆炸中造成的 简易爆炸装置。爆炸影响了所有美国军队的军人 即使没有明显或广泛的爆炸暴露。接触过 TBI 的个人可能会经历 头痛和学习障碍等疾病，并且患长期疾病的风险可能增加，例如 神经退行性疾病或精神疾病 爆炸介导的 TBI 也会导致视觉功能障碍 受影响的个人。 TBI 引起的视觉功能障碍包括光敏感性、眼球运动的变化 功能障碍、视神经病变和视网膜病变，以及皮质损伤导致的同向视野丧失。甚至 患有轻度 TBI 的患者经常报告视力困难和视觉生活质量下降，但这些并非正常现象。 通过常规眼科检查发现。这些症状可能代表眼睛和大脑的亚临床疾病， 这是未被充分报道的，并且可能会发展为更严重的视力缺陷。虽然视觉和认知上 冲击波暴露后缺陷明显，但视网膜损伤和大脑损伤之间的关系尚未确定 已被描述，并且不确定爆炸损伤后的视力损伤是否是直接视网膜损伤、视神经损伤的结果。 神经损伤，或由于大脑视觉处理中心神经元损失而导致的逆行性变。 建立这种关系对于开发康复疗法至关重要，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也很困难 以及爆炸暴露后实验室模型中的视觉认知关系。 该提案解决了阻碍改善退伍军人生活质量的两个需求 康复。首先是临床前啮齿动物模型缺乏视觉和视觉认知测试结果 准确反映人类视觉处理。此类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转化指标 生活。我们的提案旨在提供这样一个临床前啮齿动物模型。二是缺乏非侵入性， 视功能的非药物康复。我们的建议将通过确定是否 经颅直流电刺激 (tDCS) 可以利用内源性神经元可塑性来恢复视力 功能。 我们的中心假设首先是爆炸介导的 TBI 会导致突触失调，从而损害 神经元有效发挥作用的能力。其次，我们假设 tDCS 在视觉康复过程中应用 治疗将改善视觉结果，从而改善视觉认知关系和质量 生活。我们将使用 TBI 后的视觉和视觉认知关系的新结果来分析这些结果 除了了解如何康复之外，还反映退伍军人的困难和生活质量的方式 这种功能障碍。