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：
9188085
负责人：
James JASON McAnany
金额：
$ 39.98万
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 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9188085
关键词：
Address Affect Characteristics Clinical Clinical Trials Cone Contrast Sensitivity Data Diabetes Mellitus Diabetic Retinopathy Disease Electrophysiology (science)Electroretinography Eye diseases Frequencies Functional disorder Image Impairment Investigation Letters Light Location Measurement Measures Modeling Nature Nerve Degeneration Neuronal Dysfunction Noise Optical Coherence Tomography Patients Pattern Photoreceptors Play Process Psychophysics Reporting Research Retina Retinal Retinal Cone Retinal Diseases Site Source Structure Structure-Activity Relationship Techniques Testing Therapeutic Intervention Thinness Time Treatment Efficacy Vision Visual Visual Pathways Visual Psychophysics base central visual field clinical application diabetic diabetic patient functional loss improved indexing insight luminance macula novel novel strategies novel therapeutic intervention patient subsets prevent public health relevance quantum receptor relating to nervous system response retinal neuron targeted treatment therapy outcome tool treatment trial vascular abnormality

项目摘要

DESCRIPTION (provided by applicant): There is mounting evidence that diabetes mellitus affects retinal neurons before abnormalities of the retinal vasculature are apparent clinically. However, relatively little is known about these neural deficits and how they affect visual function in diabetic patients who have minimal or no clinically-apparent diabetic retinopathy (M/N DR). The objective of this proposal is to develop and apply novel approaches for characterizing the nature and extent of visual dysfunction and its potential relationship to neural processes in M/N DR patients. Achieving this objective will provide important new insight into neural dysfunction in patients who have M/N DR and will establish new tests that are capable of classifying patients who have not yet developed clinically- apparent retinopathy, a group that cannot be staged or subtyped according to standard scales. This new insight and the ability to subtype these patients would be of great use in clinical trials that aim to slow or prevent neurodegeneration. Three complementary aims are proposed that use imaging, psychophysical, and electrophysiological techniques to provide new views of retinal function and structure in M/N DR patients and to address important questions generated by our preliminary investigations: Aim 1 will determine the relationship between contrast sensitivity deficits and retinal structure in M/N DR patients by simultaneously acquiring microperimetric contrast sensitivity measurements and optical coherence tomography measurements. Aim 2 will identify the mechanisms underlying electrophysiological abnormalities in these patients by measuring the electroretinogram (ERG) using standard full-field brief flashes of light, contrast- modulated sinewave flicker, focal maculr ERGs, and multi-focal ERGs. This comprehensive battery of electrophysiological tests will be used to challenge common assumptions regarding the sites of disease action that underlie ERG abnormalities. Aim 3 will measure and model contrast sensitivity deficits in diabetic patients who have M/N DR using a visual-luminance-noise-based paradigm that will provide insight into sites and mechanisms of disease action. After accomplishing these aims, we will have: 1) established clinically-applicable approaches to vision assessment that can quantify neural abnormalities in diabetic patients who have M/N DR; 2) gained new insight into the sites and mechanisms that underlie impairments in visual function in these patients. This line of study is particularly important and timely as new therapeutic approaches for treating early- stage retinopathy are being investigated, but the tools that are currently available to subtype patients and evaluate therapeutic efficacy lag behind.

描述（由申请人提供）：越来越多的证据表明，在临床上出现明显的视网膜脉管系统异常之前，糖尿病会影响视网膜神经元。然而，人们对这些神经缺陷及其如何影响视觉功能知之甚少。该提案的目的是开发和应用新方法来表征 M 中视觉功能障碍的性质和程度及其与神经过程的潜在关系。 /N DR 患者的实现将为神经功能障碍提供重要的新见解。患有 M/N DR 的患者将建立新的测试，能够对尚未出现临床明显视网膜病变的患者进行分类，该组无法根据标准量表进行分期或亚型。这种新的见解和对这些患者进行亚型分类的能力。患者将在旨在减缓或预防神经退行性变的临床试验中发挥重要作用，提出了三个互补的目标，即使用成像、心理物理学和电生理学技术来提供 M/N DR 患者视网膜功能和结构的新观点并解决这些问题。我们的初步研究产生的重要问题：目标 1 将通过同时获取微视野对比敏感度测量和光学相干断层扫描测量来确定 M/N DR 患者对比敏感度缺陷和视网膜结构之间的关系，目标 2 将确定 M/N DR 患者中电生理异常的机制。通过使用标准全场短暂闪光、对比调制正弦波闪烁、局灶性黄斑 ERG 和多焦点测量视网膜电图 (ERG) 来对这些患者进行治疗ERG。这种全面的电生理学测试将用于挑战有关 ERG 异常的疾病作用部位的常见假设，目标 3 将使用视觉亮度测量和模拟患有 M/N DR 的糖尿病患者的对比敏感度缺陷。基于噪声的范式将提供对疾病作用部位和机制的深入了解在实现这些目标后，我们将：1）建立临床适用的视力评估方法，可以量化糖尿病患者的神经异常。患有 M/N DR；2) 对这些患者视功能损伤的部位和机制有了新的认识，因为正在研究治疗早期视网膜病变的新治疗方法，但这一研究尤为重要和及时。目前可用于亚型患者和评估治疗效果的工具滞后。