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1 From the Department of Ophthalmology and 4 Lipid Research Laboratory, Emory University School of Medicine, Atlanta, Georgia; the 2 Department of Ophthalmology, University of Heidelberg, Germany; and the 3 Department of Ophthalmology, University of Alabama at Birmingham.
PURPOSE. To examine the histologic and ultrastructural changes in Bruchs membrane (BM) in apolipoprotein E deficient [ApoE(-)] mice in comparison with age-matched control animals.
METHODS. Two-month-old (group 1) and 8-month-old (group 2) normal control C57BL/6 mice and 2-month-old (group 3) and 8-month-old (group 4) ApoE(-) mice were studied. All groups of mice were fed a standard rodent diet. The mice were killed, serum lipid levels were determined, and the eyes were ultrastructurally examined using standard techniques to measure the thickness of BM. The area fraction of electron-lucent (EL) particles in BM was quantified using point-counting stereology.
RESULTS. The serum cholesterol levels of the ApoE(-) mice were significantly
higher than those of the control mice (P = 0.0001).
There was a significant thickening and EL particle accumulation in BM
associated with age in the control animals. Group 2 had a thicker BM
and more EL particle accumulation than group 1 (P =
0.0410 for thickness; P = 0.0042 for particle
accumulation). Age-related changes were not seen in ApoE(-) mice;
thickness and accumulation were similar in groups 3 and 4
(P = 0.50, thickness; P
1.0,
accumulation). Significant thickening and accumulation were seen in
young ApoE(-) mice (group 3) versus young control animals (group 1;
P = 0.008, thickening; P < 0.0001, EL
particle accumulation). Group 4 ApoE(-) mice did not have a thicker BM
or more EL particles than group 2 control animals (P =
0.2910, thickness; P = 0.35, EL particle accumulation).
"Membrane-bounded" material (material between two membranes) was
present significantly more frequently in ApoE(-) mice.
CONCLUSIONS. ApoE(-) mice exhibit accumulation of EL particles at an earlier age and have more membrane-bounded material in BM than control mice. This material has ultrastructural similarities to basal linear deposit, which accumulates in age-related maculopathy.
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