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%的美国人口患有糖尿病，另有8600万人正在接受治疗 糖尿病前期。除此之外，每四名接受退伍军人管理局护理的退伍军人中就有一名正在接受治疗 糖尿病及其许多身体并发症，超过一半的人患有糖尿病 视网膜病变。使糖尿病视网膜病变成为退伍军人的高医疗负担疾病 人口。糖尿病视网膜病变是视网膜的一种微血管病变，是 导致全世界劳动年龄人口失明的原因。在如此健康的情况下 影响，需要新的治疗方法来跟上构成的财务和身体威胁 被这种视觉疾病。这种治疗靶点最有希望的来源之一就是 免疫系统。免疫系统的改变在很大程度上介导了该病的发病 糖尿病并发症通过蛋白细胞因子的产生，其中IL-17A是最重要的 常见的细胞因子参与糖尿病的发生和发展。在我们之前的研究中， 我们发现，糖尿病导致IL-17A的产生，从而加剧了视网膜炎症， 氧化应激、血管损伤与非增殖性糖尿病视网膜病变的发病 糖尿病的小鼠模型。在目前的研究中，我们将检查IL-17A是否发挥同样的作用 病理在非增殖型糖尿病视网膜病变、增殖型糖尿病进展中的作用 我们的退伍军人管理局患者的视网膜病变和糖尿病黄斑水肿。此外，以前的癌症研究 为IL-17A诱导抗血管内皮生长因子耐药提供证据。在这里我们将检查IL-17A是否 在糖尿病抗血管内皮生长因子治疗无效的患者中起到同样的作用 视网膜病变。综上所述，这些研究将确定IL-17A在发病和死亡中的作用。 糖尿病视网膜病变的进展，同时潜在地确定一种新的视网膜治疗方法 发病机制。