Mice that produce ApoB100 lipoproteins in the RPE do not develop drusen yet are still a valuable experimental system

Masashi Fujihara, Marisol Cano, James T. Handa

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Mice typically produce apolipoprotein B (apoB)-48 and not apoB100. Apolipoprotein B100 accumulates in Bruch’s membrane prior to basal deposit and drusen formation during the onset of AMD, raising the possibility that they are a trigger for these Bruch’s membrane alterations. The purpose herein, was to determine whether mice that predominantly produce apoB100 develop features of AMD.

Methods. The eyes of mice that produce apoB100 were examined for apoB100 synthesis, cholesteryl esterase/filipin labeling for cholesteryl esters, and transmission electron microscopy for lipid particles and phenotype.

Results. Apolipoprotein B100 was abundant in the RPE-choroid of apoB100, but not wild-type mice by Western blot analysis. The apolipoprotein B100,35S-radiolabeled and immunopre-cipitated from RPE explants, confirmed that apoB100 was synthesized by RPE. Apolipopro-tein B100, but not control mice, had cholesteryl esters and lipid particles in Bruch’s membrane. Immunoreactivity of ApoB100 was present in the RPE and Bruch’s membrane, but not choroidal endothelium of apoB100 mice. Ultrastructural changes were consistent with aging, but not AMD when aged up to 18 months. The induction of advanced glycation end products to alter Bruch’s membrane, did not promote basal linear deposit or drusen formation.

Conclusions. Mice that produce apoB100 in the RPE and liver secrete lipoproteins into Bruch’s membrane, but not to the extent that distinct features of AMD develop, which suggests that either additional lipoprotein accumulation or additional factors are necessary to initiate their formation.

Original languageEnglish (US)
Pages (from-to)7285-7295
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number11
DOIs
StatePublished - 2014

Keywords

  • Age-related macular degeneration
  • Aging
  • Apolipoprotein B
  • Lipoproteins
  • Retinal pigmented epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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