title: Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase.
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 lipase-deficient 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-galactose-treated mice retained lipoproteins in the retinal pigment epithelial and Bruch's membrane to a greater extent than either PBS- or phenacylphiazolium bromide/D-galactose-treated mice at 24 and 72 hours after injection (P ≤ 0.04). Immunolabeling for carboxymethyllysine, biglycan, and lipoprotein lipase was found in D-galactose-treated 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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Marisol
authors.initials: M
authors.lastname: Cano
authors.forename: Natalia
authors.initials: N
authors.lastname: Fijalkowski
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kondo
authors.forename: Sonny
authors.initials: S
authors.lastname: Dike
authors.forename: James
authors.initials: J
authors.lastname: Handa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016570:Bruch Membrane / Q000378:metabolism*; D005260:Female; D005690:Galactose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008954:Models, Biological; D013997:Time Factors
chemical_list: D017127:Glycation End Products, Advanced; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008071:Lipoprotein Lipase; D005690:Galactose