Role of Leukocyte-endothelial Adhesion in Diabetic Retinopathy

白细胞-内皮粘附在糖尿病视网膜病变中的作用

• 批准号: 8884292
• 负责人: MICHAEL A. GRASSI
• 金额: $ 40.85万
• 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: 2015-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884292
• 关键词: Adhesions; Affect; Age; Area; Biological Markers; Blindness; Blood Vessels; Blood capillaries; Cardiovascular Diseases; Chronic; Clinical; Clinical Data; Clinical Research; Complications of Diabetes Mellitus; Development; Diabetes Mellitus; Diabetic Nephropathy; Diabetic Retinopathy; Diagnosis; Disease; Endothelium; Epidemiology; Genetic; Genetic Predisposition to Disease; Human; Hyperglycemia; Individual; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Injury; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Kidney Diseases; Leukocytes; Mediating; Microvascular Dysfunction; Neuropathy; Nutrient; Observational Study; Outcome; Pathogenesis; Patients; Play; Population; Prevalence; Process; Property; Randomized Clinical Trials; Retina; Retinal; Retinal Diseases; Risk; Risk Factors; Robotics; Role; Running; Sampling; Severities; Site; Staging; Study Subject; Testing; Time; United States; Ursidae Family; Variant; Work; capillary; chemokine; clinically relevant; clinically significant; cohort; diabetes control; diabetic; follow-up; glycemic control; high throughput screening; human subject; human tissue; inflammatory marker; innovation; macrovascular disease; macular edema; microvascular pathology; novel; proband; prospective; public health relevance; response; screening; trait

 DESCRIPTION (provided by applicant): Diabetes induces a systemic low-grade chronic inflammatory response. Leukocytes are a key mediator of inflammation throughout the body. In the setting of diabetes leukocyte aggregation and adhesion are increased at sites of retinal microvascular dysfunction. Worsening degrees of diabetic retinopathy correlate with increasing amounts of leukocyte endothelial adhesion. The objective of this proposal is to assess whether differences in leukocyte endothelial adhesion between individuals with diabetes contribute to diabetic retinopathy outcomes. The study will determine whether leukocyte endothelial adhesion represents an independent risk factor for diabetic retinopathy. While it is recognized that leukocyte mediated inflammation plays an important role in the pathogenesis of diabetic retinopathy, its relevance and clinical importance are presently unknown. The hypothesis of this study is that leukocyte endothelial adhesion represents a novel biomarker for diabetic retinopathy. Specifically, this proposal will test whether leukocyte endothelial adhesion 1) Is associated with different stages of diabetic retinopathy severity; 2) Is affected by intensive glycemic control, cumulative glycemia, diabetes duration or other factors; 3) Predicts the progression of diabetic retinopathy; or 4) Is associated with other micro and macro vascular complications including nephropathy, neuropathy and cardiovascular disease. The study objectives will be accomplished through the use of a large prospective clinical study of well-characterized human subjects with diabetic retinopathy. Accordingly, this study will leverage samples from all 1,441 subjects of the DCCT/EDIC cohort, a landmark clinical study of diabetic retinopathy. The DCCT/EDIC study prospectively followed subjects over a twenty-five year period. Access to disease relevant human tissue associated with exquisitely characterized prospective clinical data from thousands of human subjects with diabetic retinopathy is invaluable. An innovative high-throughput assay will be used to determine individual levels of leukocyte endothelial adhesion for all 1,441 DCCT/EDIC study subjects. In summary, this proposal will use human samples from a large clinical study to determine whether a novel cellular property, leukocyte endothelial adhesion, correlates with diabetic retinopathy outcomes. The ability to study and treat diabetic retinopathy has been hampered considerably by lack of a unique, valid and translatable biomarker for the disease. If successful, work from this study would establish an individual's level of leukocyte endothelial adhesion as a novel biomarker and independent risk factor for diabetic retinopathy. Such findings could have immediate clinical implications that bear on the diagnosis, management, and treatment of this condition.

 描述（由申请人提供）：糖尿病诱发全身低度慢性炎症反应。白细胞是全身炎症的关键介质。在糖尿病的情况下，视网膜微血管功能障碍部位的白细胞聚集和粘附增加。糖尿病视网膜病变的恶化程度与白细胞内皮粘附量的增加相关。该提案的目的是评估糖尿病患者之间白细胞内皮粘附的差异是否会导致糖尿病视网膜病变的结果。该研究将确定白细胞内皮粘附是否是糖尿病视网膜病变的独立危险因素。虽然人们认识到白细胞介导的炎症在糖尿病视网膜病变的发病机制中起着重要作用，但其相关性和临床重要性目前尚不清楚。这项研究的假设是，白细胞内皮粘附代表了糖尿病视网膜病变的一种新生物标志物。具体来说，该提案将测试白细胞内皮粘附是否与糖尿病视网膜病变严重程度的不同阶段相关；1）是否与糖尿病视网膜病变严重程度相关； 2) 受强化血糖控制、累积血糖、糖尿病病程或其他因素影响； 3）预测糖尿病视网膜病变的进展； 4) 与其他微血管和大血管并发症相关，包括肾病、神经病和心血管疾病。研究目标将通过对患有糖尿病视网膜病变的人类受试者进行一项大型前瞻性临床研究来实现。因此，这项研究将利用来自 DCCT/EDIC 队列的所有 1,441 名受试者的样本，这是一项具有里程碑意义的糖尿病视网膜病变临床研究。 DCCT/EDIC 研究对受试者进行了二十五年的前瞻性跟踪。获得与来自数千名糖尿病视网膜病变人类受试者的精确表征的前瞻性临床数据相关的疾病相关人体组织是非常宝贵的。将使用创新的高通量测定来确定所有 1,441 名 DCCT/EDIC 研究对象的白细胞内皮粘附个体水平。总之，该提案将使用大型临床研究的人体样本来确定一种新的细胞特性，即白细胞内皮粘附，是否与糖尿病视网膜病变的结果相关。由于缺乏针对该疾病的独特、有效和可转化的生物标志物，研究和治疗糖尿病视网膜病变的能力受到了相当大的阻碍。如果成功，这项研究的工作将确定个体白细胞内皮粘附水平作为糖尿病视网膜病变的新型生物标志物和独立危险因素。这些发现可能对这种疾病的诊断、管理和治疗产生直接的临床影响。