| A Rat Model for Studying the Biological Effects of Circulating LDL in the Choriocapillaris-BrM-RPE Complex. | |
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MedLine Citation:
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PMID: 22107828 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Retention of apolipoprotein B-containing lipoproteins in Bruch's membrane (BrM) is believed important in early age-related macular degeneration (AMD). The origin of the lipoproteins in BrM is a hot topic in AMD research. Some studies hypothesize an intraocular origin. BrM is in direct contact to the choriocapillaris; a plasma origin has also been suggested for the low-density lipoprotein (LDL) particles. We developed an animal model to study the biological effects of circulating LDL on the retina. After injection of LDL for 7 days, our results showed evidence of circulating apolipoprotein B100 retention in BrM and showed induction of early AMD-like alterations in the rat retina, such as thickening of BrM, photoreceptor TUNEL-positive cells, and inflammatory cell infiltration. In vitro assays showed that oxidized LDL (ox-LDL) treatment decreased ARPE-19 cell viability in a dose-dependent manner and that 10 mg/L ox-LDL induced marked apoptosis. The ratio of matrix metalloproteinase-2 to tissue inhibitors of metalloproteinase-3 was dysregulated after LDL and ox-LDL treatment in ARPE-19 cells, which can produce profound changes in the extracellular matrix, including thickening of and deposit formation in BrM. The observation that circulating LDL may be a significant, but not complete, origin of the lipoprotein in BrM suggests that these findings can be readily exploited for the development of new model systems and the future benefit of patients with AMD. |
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Authors:
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Lili Yin; Yuhua Shi; Xiaojuan Liu; Hongmei Zhang; Yuanyuan Gong; Qing Gu; Xingwei Wu; Xun Xu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-19 |
Journal Detail:
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Title: The American journal of pathology Volume: - ISSN: 1525-2191 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Ophthalmology, Shanghai First People's Hospital, Medical School, Shanghai Jiaotong University, Shanghai, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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