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Michaela K. Mathews; Choroidal Changes In The LDL-Receptor-Deficient Mouse Model Of Hyperlipidemia and Atherosclerosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4079.
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Ocular atherosclerosis within the choroidal vasculature may contribute to the pathology of a variety of ocular diseases, including age-related macular degeneration and non-arteritic anterior ischemic optic neuropathy. We wanted to examine whether there are choroidal lipid deposits in a mouse model of hyperlipidemia and atherosclerosis: the C57/BL6 low-density lipoprotein receptor deficient (LDLR -/-) transgenic mice, which develop aortic atherosclerosis when fed a high-fat ("western") diet.
LDLR (-/-) mice were fed a high-fat ("western") diet. After one, two, and four months respectively, serum cholesterol and LDL levels were measured and animals were euthanized. Eyes were enucleated and either cryopreserved or paraffin-embedded. In addition, aorta, liver, kidney, and heart tissues were also removed and preserved for use in various analyses. Histological and immuno-histochemical staining for lipid, LDL, apoprotein B-100 (the protein component of LDL), and markers of atherosclerosis, including macrophages and plasminogen were performed. Sections were examined by light and fluorescent microscopy. Staining patterns and intensity were compared between LDLR -/- animals fed the western diet and same-age LDLR -/- animals fed a regular rodent diet.
LDLR-/- transgenic mice exhibited lipid and lipoprotein deposition in the choroidal vasculature of the eye after being fed a "western" diet for at least two months. There were no deposits or vascular changes noticed in LDLR -/- mice prior to this time point or in LDLR -/- mice on a regular diet. Additional validation of these findings was provided by showing similar staining patterns in other organs of the same animals, as has been previously reported.
The LDL-receptor-deficient mouse model is well suited for studying choroidal atherosclerosis and inflammation caused by hyperlipidemia. Preliminary studies show deposition of lipid and lipoprotein in the choroidal vasculature of LDLR -/- mice after two months on a "western" diet. Additional studies are under way to further define the pattern and nature of the choroidal changes.
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