Does Vision Loss Affect Tauopathy in the Brain

视力丧失是否会影响大脑中的 Tau 蛋白病

• 批准号: 10670631
• 负责人: Fan Xia
• 金额: $ 24万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670631
• 关键词: Abbreviations; Acceleration; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease risk; Amyloid beta-Protein; Anatomy; Animal Experiments; Atrophic; Attenuated; Axon; Axonal Transport; Blindness; Brain; Brain region; Cataract; Cataract Extraction; Cells; Central Nervous System; Cerebrospinal Fluid; Clinical Research; Cognitive; Confounding Factors (Epidemiology); Consensus; Darkness; Dementia; Deposition; Development; Diagnostic; Disease; Electroretinography; Excitatory Postsynaptic Potentials; Eye; FTD with parkinsonism; Family member; Fiber; Financial cost; Foundations; Functional disorder; Glaucoma; Gliosis; Hippocampus; Human; Immunohistochemistry; Impaired cognition; Impairment; Injury; Investigation; Knowledge; Lateral Geniculate Body; Life; Link; Long-Term Potentiation; Mediating; Memory Loss; Microtubule Stabilization; Microtubule-Associated Proteins; Modeling; Monoclonal Antibodies; N-Methylaspartate; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Dysfunction; Neuronal Injury; Neurons; Pathologic; Pathology; Pathway interactions; Patients; Phosphate Buffer; Physiologic Intraocular Pressure; Pick Disease of the Brain; Play; Polymers; Progressive Supranuclear Palsy; Protein Family; Reporting; Research Personnel; Retina; Retinal Diseases; Retinal Ganglion Cells; Risk; Role; Saline; Societies; Tauopathies; Testing; Thinness; Time; Vision; Visual; Visual Pathways; Visual impairment; aging population; base; cohort; corticobasal degeneration; dementia risk; excitotoxicity; glial activation; hyperphosphorylated tau; injured; member; mouse model; neovascular; neural network; novel; object recognition; polymerization; preclinical study; prevent; psychosocial; response; retinal nerve fiber layer; retinal neuron; sensory system; tau Proteins; tau aggregation; tau-1; visual deprivation

Does Vision Loss Affect Tauopathy in the Brain SUMMARY Tau is a member of the microtubule-associated proteins family, which is mainly expressed by neurons, especially in their axons where it controls the polymerization and stabilization of the microtubules and regulates axonal transport. Tauopathies, characterized by abnormal intracellular accumulation of aggregated and/or hyperphosphorylated tau within neurons, is a hallmark of Alzheimer's disease (AD) and a number of other disorders including frontotemporal dementia with parkinsonism-17 (FTDP-17), Pick disease, progressive supranuclear palsy and corticobasal degeneration. Tauopathies are among the most crippling conditions that affect our rapidly growing aging population. Due to the lack of effective diagnostics, preventative means, and treatments, these diseases significantly impair the daily life of patients and markedly impose financial costs to them, their family members and society. The retina is an extension of the neural network of the brain. It shares many similar pathophysiological changes and underlying mechanisms with the brain during neurodegenerative diseases including AD. Growing consensus among researchers and clinicians is that the interdependency of eye and brain maybe more intricate than we thought. While dysfunction of the central nervous system (CNS) will influence visual function in different ways, emerging evidence suggests that visual impairment may contribute to neurodegeneration in the brain. Multiple cohort clinical studies demonstrate that visual-impairment diseases including glaucoma and cataract increase risk of developing dementia and AD, and cataract extraction is significantly associated with lower risk of dementia development. However, conflicting studies remain. Considering clinical studies cannot control for confounding variables such as age, the stage when cognitive impairment becomes noticeable, and the extent of visual impairment, it is not surprising that conflicting results were reported, and a cause-and-effect relationship from vision loss to AD could not be tested. Therefore, we propose to use well-controlled animal experiments to test the hypothesis that visual impairment accelerates tauopathy in the brain. We will test this hypothesis using two distinct visual impairment models that model retinal neuronal injury and visual deprivation as seen in glaucoma and cataract, respectively, but at much severer extents so that we can unambiguously test the relationship between vision loss and tauopathy. This proposal is highly in line with the objectives of “NOT-AG-21-044” to “investigating how functional changes in sensory systems impact the development and progression of AD”. Completion of the proposed studies will provide important new knowledge that will fill the current knowledge gaps and provide scientific base for preventing and treating tauopathy by restoring good vision. Models developed in this project will serve as the foundation for further investigation of mechanisms by which visual loss causes neurodegeneration in tauopathy.

视力丧失会影响大脑的牵张症吗？ 摘要 Tau是微管相关蛋白家族的一员，主要由神经元表达， 尤其是在轴突中，它控制着微管的聚合和稳定，并调节 轴突运输。肌萎缩侧索硬化症，特征是细胞内聚集和/或异常聚集 神经元内过度磷酸化的tau是阿尔茨海默病(AD)和许多其他疾病的标志 疾病包括额颞叶痴呆伴帕金森综合征-17(FTDP-17)，Pick病，进展性 核上性麻痹和皮质基底部变性。肌萎缩侧索硬化症是最严重的 影响到我们快速增长的老龄化人口。由于缺乏有效的诊断、预防手段，以及 治疗，这些疾病严重损害患者的日常生活，并显著增加经济成本 他们、他们的家庭成员和社会。视网膜是大脑神经网络的延伸。IT共享 在神经退行性变过程中许多与大脑相似的病理生理变化和潜在机制 疾病包括阿尔茨海默病。研究人员和临床医生之间日益达成的共识是， 眼睛和大脑可能比我们想象的更复杂。而中枢神经系统(CNS)功能障碍 会以不同的方式影响视觉功能，新出现的证据表明，视觉障碍可能 会导致大脑中的神经退化。多项队列临床研究表明，视力障碍 包括青光眼和白内障在内的疾病会增加患痴呆症和AD以及白内障的风险 拔牙与患痴呆症的风险较低显著相关。然而，相互矛盾的研究 留下来。考虑到临床研究不能控制混杂变量，如年龄、 认知障碍变得明显，而视力障碍的程度，也就不足为奇了 报道了相互矛盾的结果，从视力丧失到AD的因果关系不可能是 测试过。因此，我们建议使用控制良好的动物实验来检验视觉的假设 损伤会加速大脑中的牵张症。我们将使用两种不同的视觉损伤来验证这一假设 模拟视网膜神经元损伤和视觉剥夺的模型，如青光眼和白内障， 但在更严格的程度上，以便我们可以明确地测试视觉之间的关系 失落和紧张症。这项提议与“NOT-AG-21-044”到“调查如何”的目标高度一致 感觉系统的功能变化影响阿尔茨海默病的发展和进展。已完成的 拟议的研究将提供重要的新知识，填补目前的知识空白，并提供 通过恢复良好的视力来防治直视病的科学依据。在此项目中开发的模型 将作为进一步研究视力丧失的机制的基础 脊椎病的神经退行性变。