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（由申请方提供）：血脂异常是糖尿病的一种重要代谢紊乱，但尚未研究血脂异常在糖尿病视网膜病变发生中的作用。视网膜具有非常特定的脂肪酸分布和代谢，与身体的其他部分不同。糖尿病对视网膜特异性脂肪酸代谢和糖尿病诱导的脂肪酸谱变化的影响尚未确定。由于n3和n6多不饱和脂肪酸（PUFA）是已知的免疫功能和炎症的调节剂，并且糖尿病视网膜病变被认为是由低度炎症条件引发的，因此我们提出以下假设。糖尿病中脂肪酸谱的变化预期使视网膜易于发生炎症，并且是糖尿病视网膜中促炎变化的起始因素。为了检验这一假设，将使用体内和体外模型解决以下特定目的： 1)描述和比较1型和2型糖尿病大鼠模型和非糖尿病对照大鼠的脂肪酸谱，这些大鼠喂食富含n3或n6 PUFA的饲料。确定富含n3和n6 PUFA的饮食对糖尿病大鼠早期炎症变化和视网膜病变发展的影响。 2)以人视网膜细胞的原代培养物为模型，确定三种主要途径的作用：（a）氧化脂质的产生;（B）转录因子的调节;和（c）脂筏结构和/或组分对n3和n6 PUFA调节基础和细胞因子诱导的ICAM-1和VCAM-1表达以及白细胞粘附的修饰。 这项工作的结果将导致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病和进展中的作用，并将提供有关具体干预策略的信息。