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. Abdelsamie, Yanchun Li, Junping Chen, Michael E. Boulton, Jian Xing Ma, Maria F. Lopes-Virella, Gabriel Virella, Timothy J. Lyons

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.-Fu, D., J. Y. Yu, M. Wu, M. Du, Y. Chen, S. A. Abdelsamie, Y. Li, J. Chen, M. E. Boulton, J-x. Ma, M. F. Lopes-Virella, G. Virella, and T. J. Lyons. Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes. J. Lipid Res. 2014. 55: 860-869.

Original languageEnglish (US)
Pages (from-to)860-869
Number of pages10
JournalJournal of Lipid Research
Volume55
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

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Pericytes
Antigen-Antibody Complex
Toxicity
Retina
Diabetic Retinopathy
Endoplasmic Reticulum Stress
oxidized low density lipoprotein
Immunoglobulin G
Apoptosis
Cytokines
IgG Receptors
Oxidative stress
Cytotoxicity
Medical problems
Type 2 Diabetes Mellitus
Oxidative Stress

Keywords

  • Aapoptosis
  • Blood retinal barrier
  • Diabetes
  • Dyslipidemia
  • Endoplasmic reticulum stress
  • Immunohistochemistry
  • Lipoprotein
  • Oxidative stress
  • Scavenger receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Medicine(all)

Cite this

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

In: Journal of Lipid Research, Vol. 55, No. 5, 2014, p. 860-869.

Research output: Contribution to journalArticle

Fu, D, Yu, JY, Wu, M, Du, M, Chen, Y, Abdelsamie, SA, Li, Y, Chen, J, Boulton, ME, Ma, JX, Lopes-Virella, MF, Virella, G & Lyons, TJ 2014, 'Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes', Journal of Lipid Research, vol. 55, no. 5, pp. 860-869. https://doi.org/10.1194/jlr.M045401
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. / Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes. In: Journal of Lipid Research. 2014 ; Vol. 55, No. 5. pp. 860-869.
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abstract = "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.-Fu, D., J. Y. Yu, M. Wu, M. Du, Y. Chen, S. A. Abdelsamie, Y. Li, J. Chen, M. E. Boulton, J-x. Ma, M. F. Lopes-Virella, G. Virella, and T. J. Lyons. Immune complex formation in human diabetic retina enhances toxicity of oxidized LDL towards retinal capillary pericytes. J. Lipid Res. 2014. 55: 860-869.",
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