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：糖尿病性视网膜病是失明的主要原因，而糖尿病性肾病是终末期肾脏疾病的主要原因。这两种状况都是糖尿病微血管疾病的表现，因此，可以从一个能够预测有疾病进展风险的患者并可以实时监测氧气供应和需求的临床工具中受益匪浅。我们将测试以下假设：使用创新的OCT方法对氧的残留代谢率进行成像，可以提供急需的，无创的生物标志物的糖尿病微血管疾病。在此提案中，我们将在健康受试者中建立一个正常的视网膜代谢率数据库，然后再检查药物治疗前后患有各种糖尿病性视网膜病变并发症的糖尿病患者。我们假设功能成像将能够解释对药物治疗的反应，并与糖尿病微血管疾病阶段相关。此外，我们将使用严格的肾功能监测来探讨抗抗氧基金对该患者人群的潜在肾脏影响。本文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NIH资助的临床科学家视网膜专家，具有视网膜成像和视网膜脉管疾病方面的特殊专业知识。 Zhang博士是NIH资助的生物医学工程师，是ANSI激光安全委员会的成员，其专业知识是功能性光学成像和新颖的残留成像工具。张博士在西北地区拥有一家成熟的实验室，与Fawzi博士共同合作，因为他们共享了一项NIH资助的研究计划。当前的提案将允许这些研究人员验证其原则动物数据。研究合作包括世界一流的眼科医生临床科学家Jampol博士。肾脏科医生，Co-I（Quaggin博士）是世界一流的临床科学家，是VEGF及其信号伴侣肾小球功能的专家。除了满足重要且与临床相关的需求外，该提案的成功还将提供定量的工具来研究残留的血流，氧气递送和提取，除了血管区域外，使研究人员能够研究视网膜几何形状与全身微血管和宏观血管障碍之间的功能关系。我们认为，我们的建议将提供患者管理的范式转变，并大大提高我们对糖尿病性视网膜病理生理学的理解。