Human Apolipoprotein E2 Transgenic Mice Show Extracellular Lipid Accumulation and Altered Expression of VEGF and bFGF in the Eyes

Abstract

Purpose: : To investigate the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age–related macular degeneration (AMD) due to extracellular lipid accumulation and angiogenesis.

Methods: : Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high fat diet for 4 weeks. Eyes were collected from the mice and extracellular lipid deposits were assessed using electron microscopy. The expression of apoE, VEGF, bFGF, and PEDF, which were molecular markers for angiogenesis, was assessed with immunohistochemistry.

Results: : Eyes of apoE2 mice, regardless of diet, contained typical extracellular lipid accumulation under electron microscopy, whereas control C57BL/6J eyes did not. Extracellular lipid accumulation was found predominantly in the retinal pigment epithelium and Bruch’s membrane and increased in the eyes of apoE2 mice after one month of a high fat diet (8 ± 2 per 50 µm² for normal chow and 11 ± 2 per 50 µm², p < 0.05). ApoE expression was similar in the apoE2 and control mice. However, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes.

Conclusions: : The eyes of apoE2 mice develop typical AMD–like extracellular lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.

Keywords: age-related macular degeneration • lipids • growth factors/growth factor receptors