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

• 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
• 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

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.

摘要 目前，9%的美国人口是糖尿病患者，另有8600万人正在接受治疗。 糖尿病前期除此之外，每四个接受退伍军人事务部护理的退伍军人中就有一个正在接受治疗。 糖尿病及其许多身体并发症，超过一半患有糖尿病 视网膜病变使糖尿病视网膜病变成为退伍军人高医疗负担的疾病 人口糖尿病视网膜病变是视网膜的一种微血管疾病， 失明的原因在世界各地的工作年龄人口。如此健康 影响，需要新的治疗方法来跟上所造成的经济和身体威胁 受到这种视觉疾病的影响。这种治疗靶点的最有希望的来源之一在于 免疫系统.免疫系统的改变介导了大部分的发病机制， 糖尿病并发症通过蛋白质细胞因子的产生，IL-17 A是最重要的 参与糖尿病发病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-17 A的产生，这增强了视网膜炎症， 氧化应激、血管损伤和非增殖性糖尿病视网膜病变的发生 糖尿病小鼠模型。在目前的研究中，我们将检查IL-17 A是否发挥同样的作用。 在非增殖性糖尿病视网膜病变、增殖性糖尿病视网膜病变、 视网膜病变和糖尿病性黄斑水肿。此外，以前的癌症研究 提供IL-17 A诱导抗VEGF药物抗性的证据。在这里，我们将检查IL-17 A是否 在对糖尿病抗VEGF治疗无反应的患者中起相同的作用。 视网膜病变总之，这些研究将确定IL-17 A在发病中的作用， 糖尿病视网膜病变的进展，同时可能确定一种新的治疗视网膜病变的方法， 发病机制