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: 10397034
• 负责人: Sina Farsiu
• 金额: $ 49.54万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397034
• 关键词: Address; Adrenal Cortex Hormones; Adult; African American population; 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; Persons; 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 眼内压（IOP）控制是一个动态过程，受常规流出组织调节。 在大多数人中，有效地维持几毫米汞中的眼内压 寿命。然而，在某些传统流出功能中的缺陷导致眼高血压，这是主要风险 视网膜神经节细胞轴突损伤和青光眼的发展因素。到目前为止，我们的理解 常规流出组织动态的依赖于间接测量或固定/处理的组织， 仅捕获信息快照。因此，体内流出动态的可视化和量化 不可能。 对于本研究，我们开发了新型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，可以直接可视化，集成和 量化活小鼠随时间的传统流出动态（一种已建立的常规模型 流出解剖学，生理和药理学）。有这样的技术，我们可以专门解决 关于衰老和青光眼中常规流出功能（DYS）功能的长期问题。当前的建议 以这样的假设为指导，即动态和集成的常规流出功能随着年龄的增长而降低 和疾病；这些是可以通过药物治疗逆转的变化，并且是可量化的。解决这个问题 假设，我们设计了三个特定的目的，以（i）检查成人的常规流出组织行为 以及老年小鼠对IOP升高或常规流出药物的质疑； （ii）监视更改 传统的流出组织行为在两种已建立的小鼠高血压模型（皮质类固醇 - 诱导和小窝蛋白1敲除）； （iii）优化新开发的OCT硬件，软件和灌注 用于更好地评估常规流出途径的技术。 这些基本实验在柔韧的模型中获得的知识将用于我们的最终目标 改善人类青光眼管理的方法，包括：早期诊断，检测流出的微小变化 功能;监测对医疗的反应，实现治疗个性化；流量映射 模式以有效地放置分流；和青光眼疾病的亚型。