Human apolipoprotein E2 transgenic mice show lipid accumulation in retinal pigment epithelium and altered expression of VEGF and bFGF in the eyes.
We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). 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 lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet (8 +/- 2 per 50 microm2 for normal chow and 11 +/- 2 per 50 microm2, 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. In conclusion, the eyes of apoE2 mice develop typical 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.
Lee
Sung-Joon
SJ
Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Institute of Biomedical Science and Safety, Korea University, Seoul 136-713, Korea.
Kim
Jeong Hun
JH
Kim
Jin Hyoung
JH
Chung
Mi Ja
MJ
Wen
Qingcheng
Q
Chung
Hum
H
Kim
Kyu-Won
KW
Yu
Young Suk
YS
D000818:Animals; D053329:Apolipoprotein E2 / Q000032:analysis / Q000502:physiology*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008268:Macular Degeneration / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D053329:Apolipoprotein E2; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2