Mechanisms of Early Functional Loss in Diabetic Eye Disease

糖尿病眼病早期功能丧失的机制

基本信息

批准号：
10711055
负责人：
James JASON McAnany
金额：
$ 18.75万
依托单位：
UNIVERSITY OF ILLINOIS 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：
2015-12-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10711055
关键词：
Address Administrative Supplement Adopted Affect Age Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease model Alzheimer’s disease biomarker Angiography Attention Award Biological Assay Biological Markers Blood Vessels Brain Central Nervous System Characteristics Clinical Clinical Trials Complications of Diabetes Mellitus Darkness Dementia Detection Diabetes Mellitus Diabetic Retinopathy Diabetic mouse Disease Early Diagnosis Early identification Electrophysiology (science)Electroretinography Eye diseases Functional disorder General Population Goals Grant Human Image Individual Knowledge Life Light Measurement Modeling Monitor Mus Mutation Nature Nerve Degeneration Neural Retina Non-Insulin-Dependent Diabetes Mellitus Optical Coherence Tomography Parents Pattern Persons Process Protocols documentation Public Health Research Resolution Retina Retinal Ganglion Cells Risk Source Structural defect Structure Testing Thick Thinness Time Translating United States National Institutes of Health cell type clinical translation cohort comparative diabetic early detection biomarkers functional loss insight interest millisecond mouse model neural non-invasive imaging novel novel strategies novel therapeutic intervention preclinical development presenilin-1 response targeted treatment therapeutic target tool vascular abnormality visual dysfunction

项目摘要

PROJECT SUMMARY Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two major public health challenges that are anticipated to grow rapidly in the coming decades. Although these two diseases may appear unrelated, there is emerging evidence that AD is a frequent complication of DM. Indeed, the risk of developing dementia is increased by 50% to 150% in people with type-2 DM compared with the general population. Importantly, mounting evidence indicates that DM and AD share retinal neurodegeneration as a core feature. Reliable, non- invasive biomarkers of early retinal neurodegeneration are needed urgently, particularly as the DM and AD fields rapidly move towards developing therapeutics that target early-stage disease. This administrative supplement will allow us to translate our novel approaches for non-invasive measurement of retinal function that have been developed under the parent award (R01EY026004; Mechanisms of Early Functional Loss in Diabetic Eye Disease) to study abnormalities of the neural retina in AD. The overarching goals of this supplement are to apply protocols and knowledge gained from our studies of retinal neurodegeneration in DM to AD, allowing us to 1) define the cellular source of retinal abnormalities in the 5xFAD mouse model of AD; 2) determine if these abnormalities provide useful biomarkers for detecting and monitoring the progression of AD. Aim 1 will characterize the nature and extent of retinal dysfunction in the 5xFAD mouse model of AD using electroretinography. Aim 2 will quantify abnormalities in retinal thickness and vascular characteristics in the 5xFAD mouse model of AD using optical coherence tomography. These studies will provide essential new knowledge regarding retinal neurodegeneration in AD and its relationship to neurodegeneration in DM. This line of study is particularly important and timely as new therapeutic approaches for treating early-stage AD are being investigated, but biomarkers that can identify early-stage AD lag behind at present.

项目概要糖尿病（DM）和阿尔茨海默病（AD）是两大公共卫生挑战预计在未来几十年内将迅速增长，尽管这两种疾病可能看起来无关，但确实存在。新的证据表明 AD 是 DM 的常见并发症。事实上，患痴呆症的风险很高。与普通人群相比，2 型糖尿病患者的患病率增加了 50% 至 150%。越来越多的证据表明 DM 和 AD 的共同核心特征是视网膜神经变性。迫切需要早期视网膜神经变性的侵入性生物标志物，特别是在 DM 和 AD 患者中各个领域迅速转向针对早期疾病的治疗方法。补充品将使我们能够转化我们用于非侵入性测量视网膜功能的新方法在家长奖下开发的（R01EY026004；早期功能丧失的机制）糖尿病眼病）研究 AD 中神经视网膜的异常。补充品旨在应用我们从 DM 视网膜神经变性研究中获得的方案和知识 AD，使我们能够 1) 定义 AD 5xFAD 小鼠模型中视网膜异常的细胞来源；2) 确定这些异常是否为检测和监测 AD 进展提供有用的生物标志物。目标 1 将使用 AD 的 5xFAD 小鼠模型来表征视网膜功能障碍的性质和程度目标 2 将量化视网膜厚度和血管特征的异常。使用光学相干断层扫描的 5xFAD 小鼠模型将提供重要的新功能。有关 AD 视网膜神经变性及其与 DM 神经变性的关系的知识。随着治疗早期 AD 的新治疗方法的出现，这一研究方向显得尤为重要和及时。正在研究中，但目前能够识别早期 AD 的生物标志物还滞后。