Quantitative assessment of glaucomatous conventional outflow dynamics

青光眼常规流出动力学的定量评估

• 批准号: 9913541
• 负责人: Sina Farsiu
• 金额: $ 51.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913541
• 关键词: Address; Adrenal Cortex Hormones; Adult; African American; Age; Aging; Anatomy; Aqueous Humor; Area; Axon; Behavior; Biological Models; Blindness; Ciliary Body; Clinical; Clinical Trials; Computer software; Cornea; Defect; Development; Diagnosis; Dimensions; Disease; Disease Progression; Distal; Early Diagnosis; Elderly; Environment; Evaluation; Eye; Future; Glaucoma; Goals; Human; Image; Iris; Knock-out; Knowledge; Measurement; Measures; Medical; Mercury; Methods; Minor; Modeling; Monitor; Morphologic artifacts; Motion; Mus; Normal Range; Ocular Hypertension; Optical Coherence Tomography; Outcome; Outcome Study; Pathology; Pathway interactions; Patients; Pattern; Penetration; Perfusion; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Physiologic Intraocular Pressure; Physiology; Pliability; Primary Open Angle Glaucoma; Procedures; Process; Research; Retinal Ganglion Cells; Risk Factors; Sampling; Sclera; Shunt Device; Structure of sinus venosus of sclera; Techniques; Technology; Testing; Thinness; Time; Tissues; Trabecular meshwork structure; Vision; Visualization; accurate diagnosis; aged; anterior chamber; automated algorithm; caveolin 1; design; disorder subtype; experimental study; genetic manipulation; image processing; improved; in vivo; individualized medicine; insight; instrumentation; millimeter; mouse model; multidisciplinary; new technology; novel; optic nerve disorder; personalized medicine; preservation; pressure; prevent; response; retinal damage; tool; treatment response

Project Summary Intraocular pressure (IOP) control is a dynamic process that is regulated by the conventional outflow tissues; effectively maintaining intraocular pressure within a couple of millimeters of mercury in most people over a lifetime. In some, however, defects in conventional outflow function result in ocular hypertension, a primary risk factor for damage to retinal ganglion cell axons and the development of glaucoma. Until now, our understanding of conventional outflow tissue dynamics has relied on indirect measurements or fixed/processed tissues, capturing only snapshots of information. Hence, visualization and quantification of outflow dynamics in vivo has not been possible. For the present study, we have developed novel perfusion methods and Optical Coherence Tomography (OCT) instrumentation, techniques, and image processing procedures that enable direct visualization, integration, and quantification of conventional outflow dynamics over time in living mice (an established model of conventional outflow anatomy, physiology, and pharmacology). Armed with such technology, we can specifically tackle longstanding questions about conventional outflow (dys)function in aging and glaucoma. The current proposal is guided by the hypothesis that the dynamic and integrated conventional outflow function diminishes with age and disease; these are changes that can be reversed by drug treatment and are quantifiable. To address this hypothesis, we have designed three specific aims to (i) Examine conventional outflow tissue behavior in adult and elderly mice challenged with IOP elevations or conventional outflow drugs; (ii) Monitor changes in conventional outflow tissue behavior in two established mouse models of ocular hypertension (corticosteroid- induced and caveolin-1 knockout); (iii) Optimize newly developed OCT hardware, software, and perfusion techniques for better evaluation of the conventional outflow pathway. Knowledge gained from these fundamental experiments in a pliable model will be used toward our ultimate goal of improving glaucoma management in humans, including: early diagnosis, detecting minor changes in outflow function; monitoring response to medical treatment, enabling personalization of treatment; mapping of flow patterns to enable effective placement of shunts; and subtyping of glaucoma disease.

项目摘要 眼压控制是一个由常规流出组织调节的动态过程； 大多数人在一年多的时间里有效地将眼压维持在几毫米汞的范围内 一辈子。然而，在一些情况下，常规流出功能的缺陷会导致高眼压，这是一种主要的风险 视网膜神经节细胞轴突受损和青光眼发生的因素。到目前为止，我们的理解是 传统的流出组织动力学依赖于间接测量或固定/处理的组织， 仅捕获信息的快照。因此，活体外流动力学的可视化和量化具有 不可能的。 在目前的研究中，我们开发了新的灌注方法和光学相干断层扫描(OCT) 仪器、技术和图像处理程序，支持直接可视化、集成和 活体小鼠体内常规流出动力学随时间的量化(已建立的常规流出动力学模型 流出解剖学、生理学和药理学)。有了这样的技术，我们可以专门解决 关于衰老和青光眼中常规流出(Dys)功能的长期问题。目前的提案 所依据的假设是动态的和综合的常规流出函数随着年龄的增长而减小 和疾病；这些变化可以通过药物治疗逆转，并且是可以量化的。要解决这个问题 假设，我们设计了三个特定的目标来(I)检查成年人的常规流出组织行为 和老年小鼠，用眼压升高或常规流出药物进行挑战；(Ii)监测 两种已建立的高眼压小鼠模型的常规流出组织行为(皮质类固醇- (Iii)优化新开发的OCT硬件、软件和灌流 更好地评价常规流出路径的技术。 从这些基础实验中获得的柔韧模型知识将用于我们的最终目标 改善人类青光眼管理，包括：早期诊断，检测流出的微小变化 功能；监控医疗响应，实现个性化治疗；绘制流程 能够有效放置分流术的模式；以及青光眼疾病的亚型。