June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Early ocular lipid deposition in a mouse model of hyperlipidemia and atherosclerosis
Author Affiliations & Notes
  • Michaela Mathews
    Ophthalmology, Univ of Maryland, Baltimore, Baltimore, MD
  • Tatyana Albukh
    Ophthalmology, Univ of Maryland, Baltimore, Baltimore, MD
  • Katherine Duncan
    Ophthalmology, Univ of Maryland, Baltimore, Baltimore, MD
  • Footnotes
    Commercial Relationships Michaela Mathews, None; Tatyana Albukh, None; Katherine Duncan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4104. doi:
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      Michaela Mathews, Tatyana Albukh, Katherine Duncan; Early ocular lipid deposition in a mouse model of hyperlipidemia and atherosclerosis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4104.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: The Lipoprotein receptor deficient (LDLR-/-) mouse a well established model for hyperlipidemia and atherosclerosis. Recently, aged LDLR-/- mice have been found to develop lipid deposits in Bruch's membrane and retinal degeneration, when fed a diet rich in lipids. These changes have been likened to atherosclerotic plaques as well as to human age-related macular degeneration(AMD). The structural changes effected by hyperlipidemia in younger LDLR-/- mice and the timing of early changes have yet to be determined. This study investigates early sub-retinal and choroidal changes caused by hyperlipidemia to explore the hypothesis that hyperlipidemia-induced lipid deposition and inflammatory changes in the eye could be a predictor of AMD and atherosclerosis later in life.

Methods: C57BL/6J-LDLR-/- and C57BL/6J wild-type control mice (total n=24) were fed either a regular rodent diet or a high-fat "western" diet. At the ages of 1-3 months and 4-8 months, respectively, animals were humanely killed. Blood was collected for determination of serum lipid concentration using a Cholesterol Assay Kit. Eyes were enucleated and fixed. Full-thickness sections of the eye, taken at the posterior pole were imaged using transmission electron microscopy (TEM). The thickness of Bruch's membrane in ten fields of the TEM grid was measured. For localization of neutral lipids and fatty streak atherosclerotic lesions, the fellow eyes were stained with oil red O and analyzed by light microscopy. Statistical analysis was performed to determine mean total Cholesterol(TC) and LDL levels as well as average Bruch's membrane thickness in each group.

Results: LDLR -/- mice had an up to twenty-fold increase of TC and a one- hundred- fold increase in LDL when compared to WT control. LDLR -/- mice on a high-calorie diet developed subretinal lipid deposits and Bruch’s membrane changes as early as one month after starting the high fat diet. Atherosclerotic and retinal degenerative changes were observed in aged, hyperlipidemic mice. Overall thickness and lipid deposits in Bruch's membrane decreased with age.

Conclusions: Diet- induced Hyperlipidemia, results in systemic atherosclerosis as well as in AMD-like lipid deposition and Bruch's membrane thickening in the eye, starting at a young age. Early detection of structural changes in the eye may have great predictive value for the development of AMD as well as for systemic atherosclerosis.

Keywords: 413 aging • 583 lipids • 438 Bruch's membrane  

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