Fu Dongxu, Yu Jeremy Y, Wu Mingyuan, Du Mei, Chen Ying, Abdelsamie Souzan A, Li Yanchun, Chen Junping, Boulton Michael E, Ma Jian-Xing, Lopes-Virella Maria F, Virella Gabriel, Lyons Timothy J
Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
J Lipid Res. 2014 May;55(5):860-9. doi: 10.1194/jlr.M045401. Epub 2014 Mar 10.
Recently it has been shown that levels of circulating oxidized LDL immune complexes (ox-LDL-ICs) predict the development of diabetic retinopathy (DR). This study aimed to investigate whether ox-LDL-ICs are actually present in the diabetic retina, and to define their effects on human retinal pericytes versus ox-LDL. In retinal sections from people with type 2 diabetes, costaining for ox-LDL and IgG was present, proportionate to DR severity, and detectable even in the absence of clinical DR. In contrast, no such staining was observed in retinas from nondiabetic subjects. In vitro, human retinal pericytes were treated with native LDL, ox-LDL, and ox-LDL-IC (0-200 mg protein/l), and measures of viability, receptor expression, apoptosis, endoplasmic reticulum (ER) and oxidative stresses, and cytokine secretion were evaluated. Ox-LDL-IC exhibited greater cytotoxicity than ox-LDL toward retinal pericytes. Acting through the scavenger (CD36) and IgG (CD64) receptors, low concentrations of ox-LDL-IC triggered apoptosis mediated by oxidative and ER stresses, and enhanced inflammatory cytokine secretion. The data suggest that IC formation in the diabetic retina enhances the injurious effects of ox-LDL. These findings offer new insights into pathogenic mechanisms of DR, and may lead to new preventive measures and treatments.
最近研究表明，循环氧化型低密度脂蛋白免疫复合物（ox-LDL-ICs）水平可预测糖尿病视网膜病变（DR）的发生。本研究旨在调查ox-LDL-ICs是否确实存在于糖尿病视网膜中，并确定其对人视网膜周细胞相对于ox-LDL的影响。在2型糖尿病患者的视网膜切片中，存在ox-LDL和IgG的共染色，其与DR严重程度成正比，甚至在无临床DR时也可检测到。相比之下，在非糖尿病受试者的视网膜中未观察到此类染色。在体外，用人天然低密度脂蛋白、ox-LDL和ox-LDL-IC（0 - 200 mg蛋白/升）处理人视网膜周细胞，并评估细胞活力、受体表达、凋亡、内质网（ER）和氧化应激以及细胞因子分泌的指标。与ox-LDL相比，ox-LDL-IC对视网膜周细胞表现出更大的细胞毒性。低浓度的ox-LDL-IC通过清道夫（CD36）和IgG（CD64）受体起作用，引发由氧化应激和内质网应激介导的凋亡，并增强炎性细胞因子分泌。数据表明，糖尿病视网膜中的IC形成增强了ox-LDL的损伤作用。这些发现为DR的发病机制提供了新见解，并可能带来新的预防措施和治疗方法。
