Aqueous Humor Dynamic Components that Determine Intraocular Pressure Variance

决定眼压变化的房水动态成分

• 批准号: 8616758
• 负责人: Sayoko E Moroi
• 金额: $ 36.39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-03 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8616758
• 关键词: Accounting; Address; Adrenergic beta-Antagonists; Age of Onset; Aqueous Humor; Biological Markers; Blindness; Circadian Rhythms; Commit; Data; Databases; Disease Progression; Dose; Drug Prescriptions; Drug usage; Environmental Risk Factor; Experimental Designs; Eye; Frequencies; Future; Glaucoma; Goals; Individual; Knowledge; Latanoprost; Linear Models; Measures; Mediating; Medical; Medicine; Modeling; Molecular; Ocular Hypertension; Office Visits; Onset of illness; Open-Angle Glaucoma; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Phase; Physiologic Intraocular Pressure; Physiological; Physiology; Placebos; Predictive Factor; Prostaglandins; Publishing; Randomized; Regimen; Risk; Staging; Testing; Time; Timolol; Treatment Efficacy; Treatment Failure; Treatment outcome; Variant; Venous Pressure level; Work; aqueous; base; cohort; follow-up; improved; new therapeutic target; response; wasting

DESCRIPTION (provided by applicant): Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and- error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, "poor response" to treatment, and large IOP fluctuation. Our objective is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs. Our central hypothesis is that individual aqueous humor dynamic components predict IOP response to medications. We will achieve our objective and work toward our goal by testing the central hypothesis through two aims. Aim 1: Test the hypothesis that aqueous humor inflow is a physiological marker of variation in timolol-mediated IOP response between individuals. Aim 2: Test the hypothesis that aqueous humor outflow is a physiological marker of variation in latanoprost-mediated IOP response between individuals. The overall experimental design will be a comprehensive comparison of physiological components of IOP in the same individual under control conditions without treatment and under experimental conditions with treatment using the two most commonly used drug classes, beta-blockers (Aim 1) and prostaglandins (Aim 2). The main outcome measures are the physiological components of IOP, namely, aqueous humor inflow, outflow facility, episcleral venous pressure, and uveoscleral outflow. The relationships among these four physiological components to IOP will be analyzed by generalized linear models. These results will provide a critically needed database on physiological components of IOP under baseline and treated conditions in the same cohort. Our team is committed to build upon these extensive physiology data from controls to the next phase by studying patients with ocular hypertension and early stages of open-angle glaucoma. Such a model would form the basis for future studies to investigate molecular and environmental interactions on IOP-based treatment outcomes and new therapeutic targets. Our results will advance understanding of IOP response variance to medications by dissecting the physiological components of drug response variations between individuals. This knowledge will bring us closer to predicting therapeutic efficacy, and decreasing treatment failures by identifying patients who are poor responders a priori. Prescribing medications based on a patient's profile of drug response will eliminate time wasted on ineffective drug prescriptions and result in more efficient medical management with fewer follow-up office visits to assess poor efficacy.

描述（由申请人提供）：青光眼是失明的主要原因。无法预测患者对药物的IOP反应是临床医生始终提供基于IOP的高效治疗的关键障碍。目前对青光眼管理的反复试验方法效率低下，并且没有解决该障碍，因为没有药物反应的预测因素。我们的长期目标是通过鉴定生物标志物和环境因素来改善结果，这些生物标志物和环境因素构成了患者按年龄增长，疾病进展速度，对治疗的“反应差”以及大量IOP波动的风险。我们的目标是通过专注于预测IOP反应对药物的生理因素来解决这一关键障碍。我们的核心假设是，个体的水性幽默动态成分预测了对药物的反应。我们将通过两个目标来测试中心假设来实现我们的目标并朝着目标努力。 AIM 1：检验以下假设：幽默流入是蒂莫洛介导的个人之间的IOP反应变异的生理标志物。 AIM 2：检验以下假设：幽默流出是latanprost介导的个人之间的IOP反应变异的生理标记。整体实验设计将是在对照条件下在同一个人中的生理成分的全面比较，而无需治疗，并且在实验条件下使用两个最常用的药物类别，β受体阻滞剂（AIM 1）和前列腺素（AIM 2）进行治疗。主要结果指标是IOP的生理组成部分，即水性幽默流入，流出设施，cass虫静脉压力和葡萄球菌流出。这四个生理组件与IOP之间的关系将通过广义线性模型进行分析。这些结果将为IOP的生理组成部分提供迫切需要的数据库，并在同一队列中处理过的条件。我们的团队致力于通过研究眼部高血压和开放角青光眼的早期阶段的患者来依靠这些广泛的生理学数据。这种模型将构成未来研究的基础，以研究基于IOP的治疗结果和新的治疗靶标的分子和环境相互作用。我们的结果将通过剖析个体之间药物反应变化的生理成分来提高对药物的反应差异的理解。这些知识将使我们更接近预测治疗功效，并通过确定较差的反应者的患者是先验的患者，从而减少治疗失败。根据患者对药物反应的概况的处方药物将消除浪费无效的药物处方的时间，并导致更有效的医疗管理，随访较少，以评估不良疗效。