Functional Retinal Imaging to Monitor Pharmaco-Therapies in 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，将极大地受益于能够预测处于疾病进展风险中的患者并且能够真实的时间监测氧气供应和需求的临床工具。我们将测试以下假设：使用创新的OCT方法对视网膜氧代谢率进行成像，可以提供急需的糖尿病微血管疾病的非侵入性生物标志物。在本提案中，我们将建立健康受试者视网膜代谢率的标准数据库，然后继续检查药物治疗前后伴有各种糖尿病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药物治疗的反应，以及与糖尿病微血管疾病的阶段。此外，我们将通过严格监测肾功能，探讨抗VEGF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，在视网膜成像和视网膜血管疾病方面具有特殊专长。Zhang博士是NIH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Fawzi博士有着密切的合作关系，因为他们共同拥有NIH资助的研究项目。目前的提案将允许这些研究人员验证他们的原理性动物数据。该研究合作包括共同我博士Jampol，一个世界级的眼科医生临床科学家。肾脏病学家，Co-I（Quaggin博士）是世界级的临床科学家和VEGF及其信号传导伙伴的肾小球功能专家。除了满足重要的临床相关需求外，该提案的成功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与系统性微血管和大血管疾病之间的功能关系。我们相信，我们的建议将提供一个范例的转变，在病人的管理，以及大大提高我们的理解的病理生理学的糖尿病视网膜病变。

 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.