Dyslipidemia and diabetic retinopathy

血脂异常和糖尿病视网膜病变

• 批准号: 6984993
• 负责人: Julia V Busik
• 金额: $ 34.83万
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984993
• 关键词: cell adhesion molecules; clinical research; diabetic retinopathy; dietary lipid; dietary supplements; human tissue; hyperlipidemia; inflammation; insulin dependent diabetes mellitus; laboratory rat; membrane lipids; membrane structure; noninsulin dependent diabetes mellitus; nutrition related tag; omega 3 fatty acid; oxidized lipid; tissue /cell culture; transcription factor; unsaturated fatty acids; vascular cell adhesion molecule; vascular endothelium

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(申请人提供)：血脂异常是糖尿病的一种突出的代谢紊乱，然而，血脂异常在糖尿病视网膜病变发展中的作用尚未被研究。与身体其他部分不同，视网膜有非常特殊的脂肪酸分布和新陈代谢。糖尿病对视网膜特异性脂肪酸代谢的影响以及糖尿病引起的脂肪酸谱改变尚未确定。由于n3和n6多不饱和脂肪酸(PUFA)是已知的免疫功能和炎症调节因子，糖尿病视网膜病变被认为是由低级别炎症条件引发的，我们提出以下假设。糖尿病患者脂肪酸谱的改变有望使视网膜易于发生炎症反应，并成为糖尿病视网膜促炎改变的始动因素。为了验证这一假设，将使用体内和体外模型处理以下特定目标： 1)研究和比较1型和2型糖尿病大鼠模型和非糖尿病对照组大鼠饲喂富含n3或n6多不饱和脂肪酸的饲料的脂肪酸组成。目的：探讨高n3、n6多不饱和脂肪酸饮食对糖尿病大鼠早期炎症变化及视网膜病变的影响。 2)以原代培养的人视网膜细胞为模型，探讨氧化脂质的产生、转录因子的调节、脂筏结构和/或成分对n3、n6多不饱和脂肪酸的调节以及细胞因子对ICAM-1和VCAM-1表达和白细胞黏附的影响。 这项工作的结果将有助于更好地了解脂肪酸的促炎和抗炎作用在糖尿病视网膜病变的发生和发展中的作用，并将为具体的干预策略提供信息。