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

基本信息

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
项目类别：
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

项目摘要

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（由申请人证明）：糖尿病是在视网膜微血管中增加了全身性低级慢性炎症反应。糖尿病会导致糖尿病性视网膜病变的结果。糖尿病性视网膜病变的生物疗法。心血管疾病将通过糖尿病患者进行大量的前瞻性临床研究与糖尿病性视网膜病的人类和人类受试者的前瞻性临床数据相关的前瞻性受试者是无价的。总而言之，该提案将使用大型临床研究中的人类样本来确定新型细胞过程，白细胞，与糖尿病性视网膜病变的结果相关和糖尿病性视网膜的独立危险因素。