Quantitative assessment of glaucomatous conventional outflow dynamics

项目摘要 眼内压（IOP）的控制是一个动态的过程，受常规流出组织的调节; 有效地将大多数人的眼内压维持在几毫米汞柱以内， 辈子然而，在某些情况下，常规流出功能的缺陷会导致高眼压，这是一种主要风险 视网膜神经节细胞轴突损伤和青光眼发展的因素。到目前为止，我们的理解 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， 只捕捉信息的快照。因此，体内流出动力学的可视化和量化具有重要意义。 是不可能的。 在本研究中，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，使直接可视化，集成， 在活小鼠中随时间的常规流出动力学的定量（常规流出动力学的建立模型） 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道（dys）功能的长期问题。现时的建议 的假设，即动态和综合的传统外流功能随着年龄的增长而减少 这些变化可以通过药物治疗逆转，并且是可以量化的。为了解决这个 假设，我们设计了三个具体的目标：（i）检查成人的常规流出组织行为 和用IOP升高或常规流出药物攻击的老年小鼠;（ii）监测 在两种建立的高眼压小鼠模型（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 更好地评价传统流出道的技术。 从这些基础实验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，包括：早期诊断，检测流出量的微小变化， 功能;监测对医疗的反应，实现个性化治疗;绘制流程图 能够有效放置分流器的模式;以及青光眼疾病的亚型。

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.