Intraretinal Leakage and Oxidation of LDL in Diabetic Retinopathy

Mingyuan Wu, Ying Chen, Kenneth Wilson, Alin Chirindel, Michael A Ihnat, Yongxin Yu, Michael E Boulton, Luke I Szweda, Jian-Xing Ma, Timothy J Lyons

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Abstract

Purpose: The pathogenesis of diabetic retinopathy (DR) is not fully understood. Clinical studies suggest that dyslipidemia is associated with the initiation and progression of DR. However, no direct evidence supports this theory.

Methods: Immunostaining of apolipoprotein B100 (ApoB100, a marker of low-density lipoprotein [LDL]), macrophages, and oxidized LDL was performed in retinal sections from four different groups of subjects: nondiabetic, type 2 diabetic without clinical retinopathy, diabetic with moderate nonproliferative diabetic retinopathy (NPDR), and diabetic with proliferative diabetic retinopathy (PDR). Apoptosis was characterized using the TUNEL assay. In addition, in cell culture studies using in vitro-modi?ed LDL, the induction of apoptosis by heavily oxidized-glycated LDL (HOG-LDL) in human retinal capillary
pericytes (HRCPs) was assessed.

Results: Intraretinal immuno?uorescence of ApoB100 increased with the severity of DR. Macrophages were prominent only in sections from diabetic patients with PDR. Merged images revealed that ApoB100 partially colocalized with macrophages. Intraretinal oxidized LDL was absent in nondiabetic subjects but present in all three diabetic groups, increasing with the severity of DR. TUNEL-positive cells were present in retinas from diabetic subjects but absent in those from nondiabetic subjects. In cell culture, HOG-LDL induced the activation of caspase, mitochondrial dysfunction, and apoptosis in
HRCPs.

Conclusions: These ?ndings suggest a potentially important role for extravasated, modi?ed LDL in promoting DR by promoting apoptotic pericyte loss.
Original languageEnglish
Pages (from-to)2679-85
Number of pages7
JournalInvestigative ophthalmology & visual science
Volume49
Issue number6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Adult
  • Aged
  • Apolipoprotein B-100
  • Apoptosis
  • Blotting, Western
  • Capillary Permeability
  • Caspase 3
  • Caspase 7
  • Cell Culture Techniques
  • Diabetes Mellitus, Type 2
  • Diabetic Retinopathy
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • In Situ Nick-End Labeling
  • Lipoproteins, LDL
  • Macrophages
  • Middle Aged
  • Oxidation-Reduction
  • Pericytes
  • Retina

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    Wu, M., Chen, Y., Wilson, K., Chirindel, A., Ihnat, M. A., Yu, Y., Boulton, M. E., Szweda, L. I., Ma, J-X., & Lyons, T. J. (2008). Intraretinal Leakage and Oxidation of LDL in Diabetic Retinopathy. Investigative ophthalmology & visual science, 49(6), 2679-85. https://doi.org/10.1167/iovs.07-1440