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

Research output: Contribution to journalArticle

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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-modified LDL, the induction of apoptosis by heavily oxidized-glycated LDL (HOG-LDL) in human retinal capillary pericytes (HRCPs) was assessed. RESULTS. Intraretinal immunofluorescence 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 findings suggest a potentially important role for extravasated, modified LDL in promoting DR by promoting apoptotic pericyte loss.

Original languageEnglish (US)
Pages (from-to)2679-2685
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

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Diabetic Retinopathy
LDL Lipoproteins
Pericytes
Macrophages
In Situ Nick-End Labeling
Apoptosis
Cell Culture Techniques
Apolipoproteins
Dyslipidemias
Caspases
Fluorescent Antibody Technique
Retina

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Wu, M., Chen, Y., Wilson, K., Chirindel, A., Ihnat, M. A., Yu, Y., ... Lyons, T. J. (2008). Intraretinal leakage and oxidation of LDL in diabetic retinopathy. Investigative Ophthalmology and Visual Science, 49(6), 2679-2685. https://doi.org/10.1167/iovs.07-1440

Intraretinal leakage and oxidation of LDL in diabetic retinopathy. / Wu, Mingyuan; Chen, Ying; Wilson, Kenneth; Chirindel, Alin; Ihnat, Michael A.; Yu, Yongxin; Boulton, Michael E.; Szweda, Luke I.; Ma, Jian Xing; Lyons, Timothy J.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 6, 06.2008, p. 2679-2685.

Research output: Contribution to journalArticle

Wu, M, Chen, Y, Wilson, K, Chirindel, A, Ihnat, MA, Yu, Y, Boulton, ME, Szweda, LI, Ma, JX & Lyons, TJ 2008, 'Intraretinal leakage and oxidation of LDL in diabetic retinopathy', Investigative Ophthalmology and Visual Science, vol. 49, no. 6, pp. 2679-2685. https://doi.org/10.1167/iovs.07-1440
Wu, Mingyuan ; Chen, Ying ; Wilson, Kenneth ; Chirindel, Alin ; Ihnat, Michael A. ; Yu, Yongxin ; Boulton, Michael E. ; Szweda, Luke I. ; Ma, Jian Xing ; Lyons, Timothy J. / Intraretinal leakage and oxidation of LDL in diabetic retinopathy. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 6. pp. 2679-2685.
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AU - Wu, Mingyuan

AU - Chen, Ying

AU - Wilson, Kenneth

AU - Chirindel, Alin

AU - Ihnat, Michael A.

AU - Yu, Yongxin

AU - Boulton, Michael E.

AU - Szweda, Luke I.

AU - Ma, Jian Xing

AU - Lyons, Timothy J.

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N2 - 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-modified LDL, the induction of apoptosis by heavily oxidized-glycated LDL (HOG-LDL) in human retinal capillary pericytes (HRCPs) was assessed. RESULTS. Intraretinal immunofluorescence 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 findings suggest a potentially important role for extravasated, modified LDL in promoting DR by promoting apoptotic pericyte loss.

AB - 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-modified LDL, the induction of apoptosis by heavily oxidized-glycated LDL (HOG-LDL) in human retinal capillary pericytes (HRCPs) was assessed. RESULTS. Intraretinal immunofluorescence 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 findings suggest a potentially important role for extravasated, modified LDL in promoting DR by promoting apoptotic pericyte loss.

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