Glaucoma Neuroimaging in Humans and Experimental Animal Models

人类和实验动物模型中的青光眼神经影像学

• 批准号: 10203996
• 负责人: Kevin C Chan
• 金额: $ 39.44万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203996
• 关键词: Adult; Animal Model; Animals; Axonal Transport; Behavior; Biological Models; Blindness; Brain; Cell Nucleus; Choline; Chronic; Clinical; Clinical assessments; Consensus; Cytidine Diphosphate Choline; Detection; Diffusion; Disease; Disease Progression; Early Intervention; Event; Experimental Animal Model; Eye; Functional Magnetic Resonance Imaging; Functional disorder; Glaucoma; Goals; Histologic; Human; Imaging Techniques; Impairment; Intervention; Long-Evans Rats; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manganese; Measurement; Measures; Metabolic; Metabolism; Methods; Modeling; Monitor; Nerve Degeneration; Neurons; Optic Disk; Optic Nerve; Optic Nerve Injuries; Optic tract structure; Optical Coherence Tomography; Oral; Outcome; Outcome Assessment; Pathogenesis; Pathway interactions; Patients; Pattern; Physiologic Intraocular Pressure; Prevalence; Process; Protons; Retina; Rodent; Role; Severity of illness; Specificity; Structure; Testing; Thick; Time; Vision; Visual; Visual Cortex; Visual Fields; Visual Pathways; Visual impairment; Visual system structure; Visualization; age related; aging population; behavioral outcome; blood oxygen level dependent; brain behavior; cholinergic; human model; in vivo; in vivo imaging; mind control; neurobehavioral; neurochemistry; neuroimaging; non-invasive imaging; normotensive; novel; preservation; public health relevance; restoration; retinogeniculate; transneuronal degeneration; visual motor; white matter

Project summary/Abstract Glaucoma is the second leading cause of blindness worldwide. The prevalence of this age-related disease is expected to increase substantially in coming years because of the aging population. Currently, the only clinically approved glaucoma intervention targets at lowering intraocular pressure (IOP). However, the exact roles of IOP elevation in glaucomatous pathogenesis remain unclear. In addition, glaucoma may continue to progress in some patients even after lowering IOP to normal levels, which indicates that additional key factors may be contributing to the disease. The goal of this project is to better understand glaucoma mechanisms by determining non-invasively and quantitatively the pathophysiological events and disease progression in the visual system using novel, multi-parametric magnetic resonance imaging (MRI) techniques in both human glaucoma patients and experimental glaucoma models. We will test the central hypothesis that glaucoma involves impairments of the brain's visual system apart from the eye. Furthermore, such impairments may be ameliorated by early neuroprotective treatments. We will investigate the structural, metabolic and functional brain changes longitudinally using the 3-Tesla human MRI scanner and the 9.4-Tesla animal MRI scanner, and relate brain MRI findings with glaucoma disease severity using retinal thickness measurements and visual outcome assessments. The project’s primary objective is to use the developed in vivo imaging model system to find out the structural-metabolic-functional brain relationships and eye-brain-behavior relationships in both humans and animal models of glaucoma for clinical and translational applications. This information will be valuable for identifying glaucoma mechanisms in the brain, monitoring glaucoma progression in the visual system, and guiding interventions to the visual system, in order to reduce the burden of this irreversible but preventable disease. The Specific Aims to be tested are as follows: Aim 1: To test the hypothesis that experimental glaucoma impairs the visual system and visuomotor behavior in rodents. We will elevate IOP to different levels and durations to determine their contributions to the structure, metabolism and function of the visual system. We will also determine whether oral choline supplements can ameliorate the neurobehavioral effects of experimental glaucoma on the visual system. Lastly, we will determine the specificity of glaucomatous damages to the visual system by comparing the neurobehavioral effects between experimental glaucoma and other retinal or optic nerve injuries over time. Aim 2: To test the hypothesis that vision loss in human glaucoma involves impairments of the visual system. Diffusion tensor MRI, proton MR spectroscopy and functional MRI at 3 Tesla will be used to determine the structural, metabolic and functional brain changes in glaucoma patients with different degrees of vision loss. The in vivo brain MRI measures will be compared with clinical assessments by optical coherence tomography of the retina and Humphrey visual field functional tests. The visual system in glaucoma will also be compared with healthy control brains and other retinal or optic nerve injuries.

项目摘要/摘要 青光眼是全球第二大致盲原因。这种与年龄相关的疾病的流行率是 由于人口老龄化，预计未来几年将大幅增加。目前，临床上唯一的 批准的青光眼干预目标是降低眼压(IOP)。然而，IOP的确切作用 青光眼发病机制中的升高仍不清楚。此外，青光眼可能会继续在 一些患者甚至在将眼压降至正常水平后，这表明额外的关键因素可能是 导致了疾病的发生。这个项目的目标是通过以下方式更好地了解青光眼的机制 非侵入性定量测定脑血管病变的病理生理事件和疾病进展 使用新的多参数磁共振成像(MRI)技术的人类视觉系统 青光眼患者和实验性青光眼模型。我们将检验青光眼的中心假说 涉及眼睛以外的大脑视觉系统的损害。此外，这种减损可能 通过早期神经保护治疗得到改善。我们将研究结构、代谢和功能 使用3特斯拉人类核磁共振扫描仪和9.4特斯拉动物核磁共振扫描仪进行大脑纵向变化，以及 应用视网膜厚度测量和视力将脑MRI表现与青光眼疾病严重程度联系起来 结果评估。该项目的主要目标是使用开发的体内成像模型系统来 找出两者的结构-代谢-功能脑关系和眼-脑-行为关系 临床和翻译应用的青光眼的人类和动物模型。这一信息将是 对确定大脑中的青光眼机制，监测青光眼的视力进展有价值 系统，并引导对视觉系统的干预，以减轻这种不可逆转的负担 可预防的疾病。要测试的具体目标如下：目标1：测试假设 实验性青光眼损害了啮齿动物的视觉系统和视觉运动行为。我们将把眼压提高到 不同的水平和持续时间来确定它们对细胞的结构、代谢和功能的贡献 视觉系统。我们还将确定口服胆碱补充剂是否可以改善神经行为 实验性青光眼对视觉系统的影响。最后，我们将确定青光眼的特异性。 比较实验性青光眼和青光眼对视觉系统的影响 随着时间的推移，其他视网膜或视神经损伤。目的2：验证人类青光眼视力丧失的假说 涉及到视觉系统的损害。扩散张量磁共振、质子磁共振波谱和功能磁共振 特斯拉将被用来确定青光眼患者的大脑结构、代谢和功能变化 有不同程度的视力丧失。活体脑核磁共振测量将与临床评估进行比较。 通过视网膜光学相干断层扫描和Humphrey视野功能测试。中的视觉系统 青光眼也将与健康对照组的大脑和其他视网膜或视神经损伤进行比较。