Effects of modified LDL and HDL on retinal pigment epithelial cells: a role in diabetic retinopathy?

被引:69
作者
Du, M. [1 ,2 ,3 ]
Wu, M. [1 ,2 ]
Fu, D. [1 ,2 ,4 ]
Yang, S. [1 ,2 ]
Chen, J. [1 ,2 ]
Wilson, K. [1 ,2 ]
Lyons, T. J. [1 ,2 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Diabet Ctr, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK 73104 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA
[4] Harbin Med Univ, Dept Immunol, Harbin, Peoples R China
关键词
Apoptosis; Autophagy; Diabetic retinopathy; ER stress; HDL; LDL; LOW-DENSITY-LIPOPROTEIN; ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE STRESS; OXIDIZED LDL; MACULAR DEGENERATION; CAPILLARY PERICYTES; ENDOTHELIAL-CELLS; GLYCATED LDL; RISK-FACTORS; BLOOD-FLOW;
D O I
10.1007/s00125-013-2986-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Blood-retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown. In human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavily-oxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5-40 mu mol/l) or 4-hydroxynonenal (4-HNE, 5-80 mu mol/l), with or without pretreatment with N-HDL or HOG-HDL. ApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures. In DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium.
引用
收藏
页码:2318 / 2328
页数:11
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