Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes
Data(s) |
01/05/2014
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Resumo |
Recently it has been shown that levels of circulating oxidized LDL immune complexes (ox-LDL-IC) predict the development of diabetic retinopathy (DR). This study aimed to investigate whether ox-LDL-IC are actually present in the diabetic retina, and to define their effects on human retinal pericytes vs. ox-LDL. In retinal sections from people with type 2 diabetes, co-staining 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 non-diabetic subjects. In vitro, human retinal pericytes were treated with native (N-) LDL, ox-LDL, and ox-LDL-IC (0-200 mg protein/l), and measures of viability, receptor expression, apoptosis, ER and oxidative stresses, and cytokine secretion were evaluated. Ox-LDL-IC exhibited greater cytotoxicity than ox-LDL towards 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. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Fu , D , Yu , J Y , Wu , M , Du , M , Chen , Y , Abdel-Samie , S A , Li , Y , Chen , J , Boulton , M E , Ma , J-X , Lopes-Virella , M F , Virella , G & Lyons , T J 2014 , ' Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes ' Journal of Lipid Research , vol 55 , pp. 860-869 . DOI: 10.1194/jlr.M045401 |
Tipo |
article |