Accumulation of lipid particles in Bruch's membrane of LDL receptor knockout mice as a model of age-related macular degeneration

Background. Atherosclerosis is a suspected risk factor for the development of neovascular age-related macular degeneration (AMD). Methods. We used a well-established murine knockout model with low-density lipoprotein (LDL) receptor deficiency for atherosclerotic vascular pathogenesis to evaluate changes in Bruch's membrane due to high cholesterol levels. Blood cholesterol levels were modified by the diet fed (standard rodent diet or high-fat diet western type). Animals were sacrificed and plasma cholesterol levels were determined. Eyes were examined by transmission electron microscopy (TEM). Results. Plasma total cholesterol levels were highest in LDL receptor-deficient mice after high-fat diet and elevated in LDL receptor-deficient mice after standard diet compared to control mice with and without special high-fat diet. While Bruch's membranes of control animals did not exhibit any visible changes by TEM even after a high-fat diet, membrane-bound translucent particles were seen in all membranes in knockout mice. The amount of these particles was substantially increased and membranes were thickened in knockout animals following high-fat diet with additional deposits of non-membrane-bound particles. Conclusion. LDL receptor-deficient mice exhibited a degeneration of Bruch's membrane with accumulation of lipid particles, which is further increased after fat intake due to elevated blood lipid levels. In our opinion, this animal model is suitable for investigating more aspects in the pathogenesis of neovascular AMD.