Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes

Dongxu Fu, Jeremy Y Yu, Mingyuan Wu, Mei Du, Ying Chen, Souzan A Abdel-Samie, Yanchun Li, Junping Chen, Michael E Boulton, Jian-Xing Ma, Maria F Lopes-Virella, Gabriel Virella, Timothy J Lyons

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22 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)860-869
Number of pages10
JournalJournal of Lipid Research
Volume55
Early online date10 Mar 2014
DOIs
Publication statusPublished - May 2014

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    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, 55, 860-869. https://doi.org/10.1194/jlr.M045401