The role of IL-17A in the onset and progression of diabetic retinopathy in VA patients

IL-17A 在 VA 患者糖尿病视网膜病变发生和进展中的作用

基本信息

批准号：
10657466
负责人：
Patricia R Taylor
金额：
--
依托单位：
LOUIS STOKES CLEVELAND VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657466
关键词：
Address Background Diabetic Retinopathy Biological Assay Blindness Blood Blood Vessels Blood capillaries Cancer Patient Caring Cells Centrifugation Chronic Clinical Research Collaborations Complications of Diabetes Mellitus Diabetes Mellitus Diabetic Retinopathy Diabetic mouse Disease Drug resistance Early treatment Enzyme-Linked Immunosorbent Assay Extravasation Eye FDA approved Ficoll Fundus Goals Health Healthcare IL17 gene Immune system Impairment Individual Inflammation Inflammatory Injury Interleukins Malignant Neoplasms Mediating Microvascular Dysfunction Operative Surgical Procedures Oxidative Stress Pathogenesis Pathologic Patients Pharmaceutical Preparations Plasma Play Population Prediabetes syndrome Production Proliferating Proteins Resistance Retina Retinal Diseases Role Severities Source System Thick Tight Junctions Treatment Factor Type 2 diabetic Vascular Endothelial Growth Factors Vascular Permeabilities Vascular Proliferation Veterans Vision Visual Vitrectomy aging population alternative treatment care burden cytokine density diabetic improved intravitreal injection macula macular edema military veteran mouse model neutrophil new therapeutic target non-diabetic novel novel therapeutics ophthalmic examination peripheral blood proliferative diabetic retinopathy ranibizumab responders and non-responders response retina blood vessel structure retinal angiogenesis screening therapeutic target

项目摘要

Abstract Currently, 9% of the US population is diabetic, and an additional 86 million are being treated for pre-diabetes. Beyond this, one in every four Veteran receiving care from the VA is being treated for diabetes and its many physical complications, with more than half suffering from diabetic retinopathy. Making diabetic retinopathy a disease with a high healthcare burden in the Veteran population. Diabetic retinopathy is a microvascular disease of the retina, and is the leading cause of blindness in the working-age population worldwide. With such a significant health impact, new therapeutics is required to stay abreast of the financial and physical threat posed by this visual disease. One of the most promising sources of such a therapeutic target lies within the immune system. The alteration of the immune system mediates much of the pathogenesis in diabetic complications through protein cytokine production, with IL-17A being one of the most prevalent cytokines involved in the onset and progression of diabetes. In our previous studies, we discovered that diabetes induced IL-17A production, which enhanced retinal inflammation, oxidative stress, vascular impairment, and the onset of non-proliferative diabetic retinopathy in murine models of diabetes. In the current study we will examine if IL-17A plays the same pathologic role in the progression of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, and diabetic macular edema in our VA patients. Further, previous cancer studies provide evidence that IL-17A induces anti-VEGF drug resistance. Here we will examine if IL-17A plays the same role in patients that do not respond to anti-VEGF treatments for diabetic retinopathy. Taken together, these studies will define the role of IL-17A in the onset and progression of diabetic retinopathy, while potentially identifying a novel therapeutic for retinal pathogenesis.

抽象的目前，美国9％的人口是糖尿病患者，另外8600万人正在接受治疗糖尿病前。除此之外，每四个退伍军人从VA接受护理对于糖尿病及其许多身体并发症，有一半以上患有糖尿病视网膜病。使糖尿病性视网膜病变为老兵具有很高的医疗保健疾病人口。糖尿病性视网膜病是视网膜的微血管疾病，是领先的全球工作年龄人口失明的原因。如此重要的健康影响，需要新的治疗剂才能与所构成的财务和身体威胁保持同步通过这种视觉疾病。这种治疗靶标的最有前途的来源之一在于免疫系统。免疫系统的改变介导了许多发病机理通过蛋白质细胞因子产生糖尿病并发症，IL-17a是最多的并发症参与糖尿病的发作和进展的普遍细胞因子。在我们以前的研究中，我们发现糖尿病诱导IL-17A产生，从而增强了视网膜炎症，在糖尿病的鼠模型。在当前的研究中，我们将检查IL-17A是否播放相同在非增生性糖尿病性视网膜病，增生性糖尿病的进展中的病理作用 VA患者的视网膜病变和糖尿病黄斑水肿。此外，先前的癌症研究提供了IL-17A诱导抗VEGF耐药性的证据。在这里，我们将检查IL-17A是否在对糖尿病抗VEGF治疗不反应的患者中起着相同的作用视网膜病。综上所述，这些研究将定义IL-17a在发作中的作用糖尿病性视网膜病的进展，同时可能识别出新型视网膜治疗性发病。