Glaucoma Neuroimaging in Humans and Experimental Animal Models

摘要 母项目的目标是开发和应用体内成像模型系统，以找出 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动物模型。利用以下公司提供的机会 这个独特的技术平台，补充项目的目标是适应这些新颖的神经成像 填补关于灯盏乙素的知识空白的工具，灯盏花素是一种黄酮类化合物，具有许多 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 系统治疗慢性眼压升高所致的实验性青光眼。结果是 这一补充项目可能有助于确定灯盏乙素是否可以作为一种可能的候选新药 治疗青光眼的神经治疗剂。 青光眼是世界范围内导致不可逆性失明的主要原因，随着年龄的增长，青光眼的发病率越来越高 人口。虽然眼压是临床上唯一可修改的危险因素，但青光眼在某些情况下可能会继续发展 患者即使在将眼压降至正常水平后也是如此，这表明其他关键因素可能起到了作用 与青光眼的发病机制有关。我们研究的主要目标是使用活体成像模型 在父提案中开发的系统，以找出结构-代谢-功能脑关系和 青光眼患者的眼-脑-行为关系。结果将对确定青光眼的发病机制有价值 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在疾病严重程度上进展到 反映行为表现。具体地说，使用灯盏花素，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 通过口服灯盏乙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 保存和修复不仅仅是降低眼压，这反过来又可以减轻这种不可逆转的负担 但是可以预防的疾病。这一补充项目的里程碑包括成功检测到(1) 磁共振成像测量的脑结构、代谢或功能改变的改善； (2)光学相干测量视网膜结构和视觉行为功能的保存 口服灯盏乙素治疗我们的实验性青光眼模型时的断层扫描和光动力学 在实验期间与假治疗组进行比较，并进行组织学证实。 该项目基于Kevin C.Chan博士(PI)的青光眼成像专业知识，以及临床和 乔尔·舒曼医学博士的翻译性青光眼洞察(Co-I)。该团队一直在合作治疗青光眼 过去10年的神经成像和神经治疗学。

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.