TY - JOUR
T1 - Advanced glycation endproduct changes to Bruch's membrane promotes lipoprotein retention by lipoprotein lipase
AU - Cano, Marisol
AU - Fijalkowski, Natalia
AU - Kondo, Naoshi
AU - Dike, Sonny
AU - Handa, James
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052475992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052475992&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2011.04.010
DO - 10.1016/j.ajpath.2011.04.010
M3 - Article
C2 - 21801873
AN - SCOPUS:80052475992
SN - 0002-9440
VL - 179
SP - 850
EP - 859
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -