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A more recent version of this article appeared on June 1, 2008
 (Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1440
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Article

Intra-retinal Leakage and Oxidation of LDL in Diabetic Retinopathy

Mingyuan Wu 1*, Ying Chen 1, Kenneth Wilson 1, Alin Chirindel 1, Michael Ihnat 2, Yongxin Yu 1, Michael E. Boulton 3, Luke I Szweda 4, Jian-xing Ma 1, and Timothy J. Lyons 1

1 Endocrinology, OUHSC, Oklahoma City, Oklahoma, United States
2 Cell Biology, OUHSC, Oklahoma, Oklahoma, United States
3 Ophthalmology and Visual Sciences, UTMB, Galveston, Texas, United States
4 Free Radical Biology and Aging Research Program, OMRF, Oklahoma City, Oklahoma, United States

* To whom correspondence should be addressed. E-mail: mingyuan-wu{at}ouhsc.edu.


  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 B 100 (ApoB100, a marker of LDL), macrophages and oxidized low density lipoprotein (LDL) was performed in retinal sections from four different groups of subjects: non-diabetic; Type 2 diabetic without clinical retinopathy; diabetic with moderate non-proliferative diabetic retinopathy (NPDR); diabetic with proliferative diabetic retinopathy (PDR). Apoptosis was characterized using the TUNEL assay. Also in cell culture studies using in vitro-modified LDL, induction of apoptosis by heavily oxidized-glycated LDL (HOG-LDL) in human retinal capillary pericytes (HRCP) was assessed. Results. Intra-retinal 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 co-localized with macrophages. Intra-retinal oxidized LDL was absent in non-diabetic subjects but present in all three diabetic groups, increasing with severity of DR. TUNEL positive cells were present in retinae from diabetic subjects, but absent in those from non-diabetic subjects. In cell culture, HOG-LDL induced activation of caspase, mitochondrial dysfunction, and apoptosis in HRCP. Conclusion. These findings suggest a potentially important role for extravasated, modified LDL in promoting DR by promoting apoptotic pericyte loss.

Key Words: diabetic retinopathy, immunocytochemistry, ox-LDL




This article has been cited by other articles:


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S. X Zhang, J. J Wang, A. Dashti, K. Wilson, M.-H. Zou, L. Szweda, J.-X. Ma, and T. J Lyons
Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein
J. Mol. Endocrinol., September 1, 2008; 41(3): 135 - 143.
[Abstract] [Full Text] [PDF]


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