Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase

Marisol Cano, Natalia Fijalkowski, Naoshi Kondo, Sonny Dike, James Handa

Research output: Contribution to journalArticle

Abstract

Lipoprotein particles accumulate in Bruch's membrane before the development of basal deposits and drusen, two histopathologic lesions that define age-related macular degeneration (AMD). We therefore, sought to determine which molecules could participate in lipoprotein retention. Wild-type or lipoprotein lipasedeficient mice were injected with low-dose d-galactose or PBS subcutaneously for 8 weeks to induce advanced glycation endproduct (AGE) formation. Some mice were also injected with the AGE breaker phenacylphiazolium bromide and d-galactose. Rhodamine-labeled low-density lipoproteins were injected into mice, and the fluorescence was measured up to 72 hours later. AGEs, proteoglycans, and other lipid-retaining molecules were evaluated by IHC. Lipoprotein lipase distribution was assessed in AMD samples by IHC. d-galactosetreated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/d-galactosetreated mice at 24 and 72 hours after injection (P ≤ 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in d-galactosetreated mice only. Mice deficient for lipoprotein lipase treated with d-galactose did not retain lipoproteins to any measureable extent. Human AMD samples had lipoprotein lipase labeling within drusen, basal deposits, and the choroid. Mice treated with d-galactose to induce AGE formation in Bruch's membrane retain intravenously injected lipoproteins. Our results suggest that lipoprotein retention in Bruch's membrane is mediated by lipoprotein lipase.

Original languageEnglish (US)
Pages (from-to)850-859
Number of pages10
JournalAmerican Journal of Pathology
Volume179
Issue number2
DOIs
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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