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Functional Retinal Imaging to Monitor Pharmaco-Therapies in Diabetic Retinopathy

功能性视网膜成像监测糖尿病视网膜病变的药物治疗

基本信息

批准号：
9038125
负责人：
Amani A Fawzi
金额：
$ 193.11万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9038125
关键词：
Area Biological Markers Biomedical Engineering Blindness Blood Circulation Blood Vessels Blood flow Clinical Clinical Trials Collaborations Complications of Diabetes Mellitus Data Databases Diabetes Mellitus Diabetic Nephropathy Diabetic Retinopathy Disease Disease Progression End stage renal failure Eye Fluorescein Angiography Functional Imaging Functional disorder Funding Genetic Markers Geometry Health Hemoglobin Homeostasis Human Hypoxia Image Imaging Device Injection of therapeutic agent Kidney Kidney Diseases Laboratories Lasers Lead Light Maintenance Maps Measurement Mediator of activation protein Metabolic Microvascular Dysfunction Monitor Ophthalmologist Optical Coherence Tomography Organ Outcome Oxygen Oxygen Consumption Patients Perfusion Peripheral Pharmaceutical Preparations Population Prevention Randomized Renal function Reproducibility Research Research Personnel Retina Retinal Retinal Diseases Risk Safety Scanning Scientist Severities Signal Transduction Specialist Staging System Testing Therapeutic Intervention Time Tissues United States National Institutes of Health Universities Validation Vascular Diseases Vascular Endothelial Growth Factors Visible Radiation absorption animal data catalyst clinical practice clinically relevant diabetic diabetic patient follow-up glomerular function high risk imaging modality improved innovation macular edema member metabolic rate non-invasive imaging novel novel therapeutic intervention optical imaging patient population podocyte programs proliferative diabetic retinopathy protective effect public health relevance relating to nervous system research study response retina blood vessel structure standard of care success tool vascular endothelial dysfunction

项目摘要

DESCRIPTION: Diabetic retinopathy is a leading cause of blindness, while diabetic nephropathy is a leading cause of end-stage renal disease. Both of these conditions are manifestations of diabetic microvascular disease and, hence, would greatly benefit from a clinical tool that is able to predict patients at risk for disease progression and can monitor oxygen supply and demand in real time. We will test the hypothesis that imaging of the retinal metabolic rate of oxygen, using an innovative OCT approach, can provide a much-needed, non- invasive biomarker of diabetic microvascular disease. In this proposal, we will establish a normative database of retinal metabolic rate in healthy subjects, before proceeding to examining diabetic patients with various complications of diabetic retinopathy before and after pharmaco-therapy. We hypothesize that functional imaging will be able to explain the response to pharmaco-therapy, as well as correlate with diabetic microvascular disease stages. In addition, we will explore the potential renal effects of antiVEGF on this population of patients using rigorous monitoring of renal function. The experiments proposed herein will capitalize on the interdisciplinary expertise of the PI's at Northwestern University. Dr. Fawzi is an NIH-funded clinician-scientist retinal specialist with special expertise in retinal imaging and retinal vasculr diseases. Dr. Zhang is an NIH-funded biomedical engineer, member of the ANSI laser safety committee whose expertise is in functional optical imaging and novel retinal imaging tools. Dr. Zhang has an established laboratory at Northwestern, with strong collaborative ties to Dr. Fawzi, as they share an NIH-funded research program. The current proposal will allow these researchers to validate their proof-of-principle animal data. The research collaboration includes co-I Dr. Jampol, a world-class ophthalmologist clinician-scientist. Nephrologist, Co-I (Dr. Quaggin) is a world-class clinician-scientist and expert on the glomerular function of VEGF and its signaling partners. In addition to fulfilling an important and clinically relevant need, succes of this proposal will provide quantitative tools to study retinal blood flow, oxygen delivery and extraction, in addition to vessel area, allowing researchers to study functional relationships between retinal vessel geometry and systemic micro- and macro-vascular diseases. We believe that our proposal will provide a paradigm shift in patient management, as well as greatly improve our understanding of the pathophysiology of diabetic retinopathy.

描述：糖尿病视网膜病变是导致失明的主要原因，而糖尿病肾病是终末期肾病的主要原因。这两种情况都是糖尿病微血管疾病的表现，因此，能够预测疾病进展风险的患者并能够实时监测氧气供应和需求的临床工具将极大地受益。我们将验证这样一种假设，即使用创新的OCT方法对视网膜氧代谢率进行成像可以为糖尿病微血管疾病提供急需的、非侵入性的生物标志物。在这个方案中，我们将建立一个健康受试者视网膜代谢率的标准化数据库，然后再对糖尿病患者进行药物治疗前后糖尿病视网膜病变的各种并发症的检查。我们假设，功能成像将能够解释药物治疗的反应，以及与糖尿病微血管病变分期相关。此外，我们将通过严格监测肾功能来探索抗血管内皮生长因子对这类患者的潜在肾脏影响。这里提出的实验将利用西北大学PI的跨学科专业知识。Fawzi博士是美国国立卫生研究院资助的临床科学家兼视网膜专家，在视网膜成像和视网膜血管疾病方面具有特殊专长。张博士是美国国立卫生研究院资助的生物医学工程师，ANSI激光安全委员会成员，其专长是功能光学成像和新型视网膜成像工具。张博士在西北大学有一个成熟的实验室，与法齐博士有着密切的合作关系，因为他们共同参与了NIH资助的一个研究项目。目前的提案将允许这些研究人员验证他们的原则证明动物数据。这项研究合作包括世界级眼科医生、临床医生兼科学家贾姆波尔博士。肾病学家Co-I(Quaggin博士)是一位世界级的临床医生，也是研究血管内皮生长因子及其信号转导伙伴肾小球功能的专家。除了满足重要和临床相关的需求外，这项提议的成功还将提供定量工具来研究视网膜血流、氧气输送和提取，以及血管面积，使研究人员能够研究视网膜血管几何形状和系统性微血管和大血管疾病之间的功能关系。我们相信，我们的建议将提供患者管理的范式转变，以及极大地提高我们对糖尿病视网膜病变的病理生理学的理解。