Dyslipidemia and diabetic retinopathy

血脂异常和糖尿病视网膜病变

• 批准号: 7271200
• 负责人: Julia V Busik
• 金额: $ 31.81万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271200
• 关键词: Address; Adhesions; Anatomy; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Blood Vessels; Cell Adhesion Molecules; Cells; Chronic; Condition; Data; Development; Diabetes Mellitus; Diabetic Retinopathy; Diet; Dietary Supplementation; Docosahexaenoic Acids; Dyslipidemias; Fatty Acids; Human; Hyperglycemia; Individual; Inflammation; Inflammatory; Insulin-Dependent Diabetes Mellitus; Intercellular adhesion molecule 1; Intervention; Lead; Lesion; Leukocytes; Membrane Microdomains; Metabolic Diseases; Metabolism; Modeling; Modification; Molecular; Outcome; Pathway interactions; Plasma; Polyunsaturated Fatty Acids; Production; Rattus; Regulation; Rest; Retina; Retinal; Retinal Diseases; Role; Route; Structure; Testing; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Cell; Work; cytokine; diabetic; diabetic rat; fatty acid metabolism; feeding; immune function; in vitro Model; in vivo; non-diabetic; oxidized lipid; prevent; transcription factor; type I and type II diabetes

DESCRIPTION (provided by applicant): Dyslipidemia represents a prominent metabolic disorder of diabetes, however the role of the dyslipidemia in the development of diabetic retinopathy has not been studied. The retina has a very specific fatty acid profile and metabolism, different from the rest of the body. The effect of diabetes on retinal specific fatty acid metabolism and diabetes induced fatty acid profile changes is not established. Since n3 and n6 polyunsaturated fatty acids (PUFA) are known modulators of immune function and inflammation and diabetic retinopathy is proposed to be initiated by low grade inflammatory conditions, we propose the following hypothesis. The changes in fatty acid profile in diabetes are expected to predispose the retina to inflammation and be an initiating factor of the pro-inflammatory changes in the diabetic retina. To test this hypothesis the following Specific Aims will be addressed using both in vivo and in vitro models: 1) To characterize and compare the fatty acid profiles of type 1 and type 2 diabetic rat models and nondiabetic control rats fed a diet rich in either n3 or n6 PUFA. To determine the effect of the n3 and n6 PUFA rich diets on the early inflammatory changes and on the development of retinopathy in diabetic rats. 2) To determine the contribution of three major pathways (a) production of oxidized lipids; (b) regulation of transcription factors; and (c) modification of lipid raft structure and/or components to n3 and n6 PUFA regulation of basal and cytokine induced ICAM-1 and VCAM-1 expression and leukocyte adhesion using primary cultures of human retinal cells as a model. The outcome of this work will lead to a better understanding of the role of pro-inflammatory and anti-inflammatory effects of fatty acids in the onset and progression of diabetic retinopathy and will provide information on specific interventional strategies.

描述（由申请人提供）：血脂异常代表糖尿病的显着代谢疾病，但是血脂异常在糖尿病性视网膜病的发展中的作用尚未研究。视网膜具有非常特异性的脂肪酸谱和代谢，与人体其余部分不同。尚未建立糖尿病对视网膜特异性脂肪酸代谢和糖尿病诱导脂肪酸概况变化的影响。由于N3和N6多不饱和脂肪酸（PUFA）是免疫功能的已知调节剂，并且建议通过低年级炎症条件引发炎症，糖尿病性视网膜病被提出以下假设。糖尿病中脂肪酸特征的变化有望使视网膜易于发炎，并且是糖尿病视网膜促炎性变化的引发因素。为了检验该假设，使用体内和体外模型将解决以下特定目标： 1）表征和比较1型和2型糖尿病大鼠模型的脂肪酸谱和非糖尿病控制大鼠喂养富含N3或N6 PUFA的饮食。为了确定N3和N6 PUFA饮食对早期炎症性变化以及糖尿病大鼠视网膜病的发展的影响。 2）确定三种主要途径的贡献（a）氧化脂质的产生； （b）调节转录因子； （c）使用人视网膜细胞的一级培养物作为模型，对基底因子和细胞因子诱导的ICAM-1和VCAM-1表达以及白细胞粘附的N3和N6 PUFA调节的脂质筏结构和/或成分的修饰。 这项工作的结果将更好地理解脂肪酸在糖尿病性视网膜病的发作和进展中的促炎和抗炎作用的作用，并将提供有关特定介入策略的信息。