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: 10330225
• 负责人: Kevin C Chan
• 金额: $ 16.95万
• 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/10330225
• 关键词: Adult; Animal Model; Animals; Award; Axonal Transport; Behavior; Behavioral; Biological Models; Blindness; Brain; Cell Nucleus; Choline; Chronic; Clinical; Clinical assessments; Consensus; Cytidine Diphosphate Choline; Detection; Diffusion; Disease; Disease Progression; Doctor of Philosophy; Early Intervention; Event; Exhibits; Experimental Animal Model; Eye; Flavonoids; Functional Magnetic Resonance Imaging; Functional disorder; Glaucoma; Goals; Herb; Histologic; Human; Image; Imaging Techniques; Impairment; Intervention; Knowledge; 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; Parents; Pathogenesis; Pathway interactions; Patients; Pattern; Performance; Physiologic Intraocular Pressure; Placebos; Prevalence; Process; Protons; Research; Retina; Risk Factors; Role; Severity of illness; 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; insight; mind control; modifiable risk; neurobehavioral; neurochemistry; neuroimaging; non-invasive imaging; normotensive; novel; parent project; preservation; restoration; retinogeniculate; tool; transneuronal degeneration; visual motor; white matter

Abstract The Aim of the parent project is to develop and apply an 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. Building on the opportunities provided by this unique technological platform, the goal of the supplementary project is to adapt these novel neuroimaging tools towards closing knowledge gaps on how scutellarin, a flavonoid that exhibits a number of neuroprotective effects on the brain and the eye, can preserve structure and function of the visual system in experimental glaucoma induced by chronic intraocular pressure (IOP) elevation. The results of this supplementary project may help determine if scutellarin can be a possible candidate as a novel neurotherapeutic agent for glaucoma treatment. Glaucoma is the leading cause of irreversible blindness worldwide with increasing prevalence due to the aging population. While IOP is clinically the only modifiable risk factor, 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 glaucomatous pathogenesis. The primary objective of our research is to use the in vivo imaging model systems developed in the parent proposal to find out the structural-metabolic-functional brain relationships and eye-brain-behavior relationships in glaucoma. Results will be valuable for identifying glaucoma mechanisms not only within the eye but also the brain’s visual system, and how they interact and progress over disease severity to reflect behavioral performance. Specifically, using scutellarin, which is one of the major constituents of the herb Erigeron breviscapus, our supplementary project will propose that neuroprotective or neuroenhancing approaches to the visual system via oral scutellarin treatment may help guide more effective strategies for visual preservation and restoration beyond IOP lowering alone, which can in turn reduce the burden of this irreversible but preventable disease. The milestones of this supplementary project include the successful detection of (1) the amelioration of structural, metabolic or functional brain changes as measured by magnetic resonance imaging; and (2) the preservation of retinal structure and visual behavioral function measured by optical coherence tomography and optokinetics, upon oral scutellarin treatment in our experimental glaucoma model when compared to the sham treatment within the experimental period, along with histological confirmations. This project is built upon the glaucoma imaging expertise of Kevin C. Chan, PhD (PI), as well as the clinical and translational glaucoma insights by Joel S. Schuman, MD (Co-I). The team has been collaborating on glaucoma neuroimaging and neurotherapeutics over the past 10 years.

摘要 本项目的主要目的是开发和应用一种活体成像模型系统， 结构-代谢-功能脑关系和眼-脑-行为关系， 用于临床和转化应用的青光眼动物模型。利用 这个独特的技术平台，补充项目的目标是适应这些新的神经成像 用于缩小关于灯盏乙素的知识差距的工具， 对大脑和眼睛的神经保护作用，可以保护视觉的结构和功能。 系统对慢性高眼压诱导的实验性青光眼的影响。的结果 这个补充项目可能有助于确定灯盏乙素是否可以作为一种新的候选药物， 用于青光眼治疗的神经治疗剂。 青光眼是世界范围内不可逆性失明的主要原因，随着年龄的增长，患病率不断增加 人口虽然IOP是临床上唯一可改变的风险因素，但青光眼在某些情况下可能会继续进展。 即使在将IOP降低至正常水平后，患者也会出现这种情况，这表明其他关键因素可能起作用 昏迷的发病机制。我们研究的主要目的是使用在体成像模型 在父母的建议中开发的系统，以找出结构-代谢-功能的大脑关系， 青光眼的眼-脑-行为关系结果将是有价值的，以确定青光眼的机制， 不仅在眼睛内，而且在大脑的视觉系统中，以及它们如何相互作用并随着疾病的严重程度而发展， 反映行为表现。具体来说，使用野黄芩苷，这是该草药的主要成分之一 灯盏细辛，我们的补充项目将提出，神经保护或神经增强 通过口服野黄芩素治疗视觉系统的方法可能有助于指导更有效的视觉治疗策略。 保存和恢复超过IOP降低单独，这反过来又可以减少这种不可逆的负担， 而是可以预防的疾病这一补充项目的里程碑包括成功探测（1） 通过磁共振成像测量的结构、代谢或功能性脑变化的改善; （2）通过光学相干测量的视网膜结构和视觉行为功能的保留 在我们的实验性青光眼模型中， 与实验期间的假处理相比，沿着组织学确认。 这个项目是建立在青光眼成像专业知识的凯文C。陈博士（PI），以及临床和 翻译青光眼见解由乔尔S. Schuman，MD（Co-I）.该团队一直在青光眼方面进行合作 神经影像学和神经治疗学在过去的10年。

项目成果

Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models.

• DOI: 10.1167/iovs.62.10.21
• 发表时间: 2021-08-02
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Colbert MK;Ho LC;van der Merwe Y;Yang X;McLellan GJ;Hurley SA;Field AS;Yun H;Du Y;Conner IP;Parra C;Faiq MA;Fingert JH;Wollstein G;Schuman JS;Chan KC
• 通讯作者: Chan KC

Glymphatic imaging and modulation of the optic nerve.

• DOI: 10.4103/1673-5374.324829
• 发表时间: 2022-05
• 期刊: Neural regeneration research
• 影响因子: 6.1
• 作者: Kasi A;Liu C;Faiq MA;Chan KC
• 通讯作者: Chan KC

Role of Structural, Metabolic, and Functional MRI in Monitoring Visual System Impairment and Recovery.

• DOI: 10.1002/jmri.27367
• 发表时间: 2021-12
• 期刊: Journal of magnetic resonance imaging : JMRI
• 作者: Sims JR;Chen AM;Sun Z;Deng W;Colwell NA;Colbert MK;Zhu J;Sainulabdeen A;Faiq MA;Bang JW;Chan KC
• 通讯作者: Chan KC

Auditory Scene Analysis Principles Improve Image Reconstruction Abilities of Novice Vision-to-Audio Sensory Substitution Users.

• DOI: 10.1109/embc46164.2021.9630296
• 发表时间: 2021-11
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

Early inner plexiform layer thinning and retinal nerve fiber layer thickening in excitotoxic retinal injury using deep learning-assisted optical coherence tomography.

• DOI: 10.1186/s40478-024-01732-z
• 发表时间: 2024-02-01
• 期刊: Acta neuropathologica communications
• 影响因子: 7.1