Mechanisms of Early Functional Loss in Diabetic Eye Disease

糖尿病眼病早期功能丧失的机制

• 批准号: 10625270
• 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
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625270
• 关键词: Address; Adult; Affect; Age; Area; Behavioral; Benchmarking; Classification; Clinical; Clinical Trials; Color; Complications of Diabetes Mellitus; Consumption; Dark Adaptation; Darkness; Diabetes Mellitus; Diabetic Retinopathy; Disease; Electrophysiology (science); Electroretinography; Eye; Eye diseases; Functional disorder; Funding; Goals; Heterogeneity; Individual; Investigation; Knowledge; Legal Blindness; Light; Link; Maps; Measures; Mediating; Modeling; Nature; Nerve Degeneration; Neuronal Dysfunction; Neurophysiology - biologic function; Outcome Assessment; Pathway interactions; Patients; Perimetry; Phase; Phototransduction; Physiologic pulse; Population; Procedures; Process; Psychophysics; Pupil; Pupil light reflex; Research; Research Personnel; Retina; Retinal Diseases; Rod; Role; Series; Shapes; Signal Transduction; Site; Source; Stimulus; Subgroup; Techniques; Testing; Therapeutic Intervention; Time; Treatment Efficacy; United States; Validation; Vascular Diseases; Vertebrate Photoreceptors; Vision; Visual Fields; Visual impairment; Work; attenuation; clinical application; clinical examination; diabetic; diabetic patient; electrical potential; experimental study; functional loss; improved; innovation; insight; legal cases; legally blind; neural; novel; novel strategies; novel therapeutic intervention; patient subsets; pre-clinical; preservation; prevent; rapid technique; receptor; receptor function; repaired; response; retinal neuron; retinal rods; targeted therapy trials; targeted treatment; therapy development; tool; treatment trial; vascular abnormality; visual dysfunction

PROJECT SUMMARY Diabetic retinopathy is the most serious ocular complication of diabetes mellitus and is the leading cause of new cases of legal blindness among working age adults in the United States There is evidence that diabetes affects retinal neurons before abnormalities of the retinal vasculature can be seen on clinical examination. However, relatively little is known about these neural deficits and how they affect visual function in diabetic patients who have mild 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 relationship to neural processes in M/N DR patients. Achieving this objective will provide important new insight into neural dysfunction in these individuals 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 existing 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 in early-stage disease. Three complementary aims are proposed that use electrophysiological, psychophysical, and pupillometric techniques to provide new views of retinal function in M/N DR patients and to address important questions generated by our preliminary investigations: Aim 1 will characterize and understand the effects of M/N DR on rod activation, inactivation, and post-receptor function. A comprehensive battery of electrophysiological tests will be used to challenge common assumptions regarding the sites of disease action that underlie ERG abnormalities. Aim 2 will develop and apply advanced psychophysical techniques for rapid characterization of rod pathway function in M/N DR subjects. Aim 3 will evaluate functional abnormalities in M/N DR subjects using novel pupillometric techniques. 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 impaired 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.

项目概要 糖尿病视网膜病变是糖尿病最严重的眼部并发症，也是导致糖尿病的主要原因 美国工作年龄成年人新增法定失明病例 有证据表明，糖尿病 在临床检查发现视网膜脉管系统异常之前，它会影响视网膜神经元。 然而，人们对这些神经缺陷以及它们如何影响糖尿病患者的视觉功能知之甚少。 患有轻度或无临床症状的糖尿病视网膜病变 (M/N DR) 的患者。该提案的目标是 开发和应用新的方法来表征视觉功能障碍的性质和程度及其 与 M/N DR 患者神经过程的关系。实现这一目标将提供重要的新见解 研究这些个体的神经功能障碍，并将建立能够对患者进行分类的新测试 尚未出现临床上明显的视网膜病变的人群，无法进行分期或亚型分类 根据现有规模。这种新的见解和对这些患者进行亚型分类的能力将非常有用 旨在减缓或预防早期疾病神经退行性变的临床试验。三个互补的目标 建议使用电生理学、心理物理学和瞳孔测量技术来提供新的观点 M/N DR 患者的视网膜功能，并解决我们的初步研究产生的重要问题 研究：目标 1 将描述并理解 M/N DR 对视杆细胞激活、失活和 受体后功能。将使用一系列全面的电生理测试来挑战常见的 关于导致 ERG 异常的疾病作用部位的假设。目标 2 将发展并 应用先进的心理物理学技术快速表征 M/N DR 中的杆状通路功能 科目。目标 3 将使用新型瞳孔测量技术评估 M/N DR 受试者的功能异常。 实现这些目标后，我们将：1）建立临床适用的视觉方法 可以量化患有 M/N DR 的糖尿病患者的神经异常的评估； 2）获得新的 深入了解这些患者视功能受损的部位和机制。本研究方向 随着治疗早期视网膜病变的新治疗方法的出现，这一点显得尤为重要和及时。 正在研究中，但目前可用于亚型患者和评估治疗的工具 功效滞后。