98th Annual Meeting DOG 2000

P 3

Ultrastructural changes in Bruch’s membrane of Apolipoprotein E-deficient mice ?

S. Dithmar1,2, C. A. Curcio3, N. A. Le4, N. Sharara1, H. E. Grossniklaus1

Purpose: To examine the histological and ultrastructural changes in Bruch’s membrane (BM) in Apolipoprotein E deficient (ApoE(-)) mice in comparison to age-matched controls.

Methods: Two-month-old (group 1) and eight-month-old (group 2) normal control C57BL/6 mice and two-month-old (group 3) and eight-month-old (group 4) ApoE(-) mice were studied. All groups of mice were fed a standard rodent diet. The mice were sacrificed, serum lipid levels were determined, and the eyes were ultrastructurally examined using standard techniques with the thickness of BM measured. 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 of the control mice (p=0.0001). There was a significant thickening and el-particle accumulation in BM associated with age in the controls. Group 2 had a thicker BM and more el-particle accumulation than group 1 (p=0.0410 for thickness; p=0.0042 for el-particle accumulation). Age associated thickening and el-particle accumulation was not seen in ApoE(-) mice, group 4 versus group 3 (p=0.50 thickness; p?1.0 el-particle accumulation). Significant thickening and accumulation was seen in young ApoE(-) mice (group 3) versus young controls (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 controls (p=0.2910 thickness; p=0.35 el-particle accumulation). Membrane-bounded material was significantly more frequent 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. These ultrastructural changes resemble basal linear deposits, which are found in human age-related maculopathy.

1Dep. of Ophthalmology and 4Lipid Research Laboratory, Emory University School of Medicine, Atlanta 2Department of Ophthalmology, University of Heidelberg, Germany, INF 400, 69120 Heidelberg, 3Dep. of Ophthalmology, University of Alabama at Birmingham
Supported by Gertrud Kusen Foundation (Di 98/99), RPB Inc., and NIH EY06360