May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Changes in Bruch's Membrane of Transgenic Mice Overexpressing ApoB100 and Biglycan Proteins - Implications for Age-Related Macular Degeneration
Author Affiliations & Notes
  • F. B. Sallo
    Division of Pathology, Institute of Ophthalmology (UCL), London, United Kingdom
  • P. J. Luthert
    Division of Pathology, Institute of Ophthalmology (UCL), London, United Kingdom
  • P. Munro
    Division of Pathology, Institute of Ophthalmology (UCL), London, United Kingdom
  • M. Santha
    Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary
  • E. Bereczki
    Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary
  • I. Lengyel
    Division of Pathology, Institute of Ophthalmology (UCL), London, United Kingdom
  • Footnotes
    Commercial Relationships  F.B. Sallo, None; P.J. Luthert, None; P. Munro, None; M. Santha, None; E. Bereczki, None; I. Lengyel, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1754. doi:https://doi.org/
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      F. B. Sallo, P. J. Luthert, P. Munro, M. Santha, E. Bereczki, I. Lengyel; Changes in Bruch's Membrane of Transgenic Mice Overexpressing ApoB100 and Biglycan Proteins - Implications for Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1754. doi: https://doi.org/.

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

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Abstract

Purpose: : Age-Related Macular Degeneration (AMD) is characterized by the accumulation of lipid- and protein-rich deposits in Bruch’s Membrane (BrM). A consequent decrease in hydraulic conductivity and impairment of transport through BrM is considered to play a central role in the pathogenesis of AMD. The mechanism of deposit formation however is not well understood. In other diseases like atherosclerosis, the interaction of ApoB100 and the extracellular matrix proteoglycan Biglycan was shown to be a key step in lipid entrapment. The aim of this study was to test the effect of the simultaneous overexpression of human ApoB100 and biglycan genes in combination with a high-cholesterol diet on BrM morphology in transgenic mice.

Methods: : 6-week-old homozygous ApoB100 (apoB+/+), Biglycan (biglycan+/+), hemizygous double transgenic (apoB+/- x biglycan+/-) and C57bl/6 female mice were fed either a standard chow or a diet supplemented with 2% cholesterol for 17 weeks. Animals were sacrificed, serum lipid levels were measured and eyes were processed for Transmission Electron Microscopy according to standard protocol. Morphometric analysis of digitally acquired TEM images of BrM was performed using Adobe PhotoShop with the FoveaPro plug-in and the ImageJ analysis package.

Results: : Double transgenic animals fed a high-cholesterol diet showed a statistically significant (p<0.05) increase in BrM thickness as well as basal deposits of a morphology compatible with basal linear deposists (BlinD). This correlated well with elevated total and LDL cholesterol levels. Biglycan transgenic animals showed a marked but diet-independent increase in BrM thickness with clear differences in BrM morphology.

Conclusions: : Our results indicate that ApoB100/biglycan interaction may indeed play a role in the pathogenesis of AMD. Biglycan may also contribute to BrM changes via pathways unrelated to lipid metabolism.

Keywords: age-related macular degeneration • lipids • proteoglycans/glycosaminoglycans 
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