Role of Leukocyte-endothelial Adhesion in Diabetic Retinopathy

点击翻译按钮获取中文摘要

 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.