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