ERG Responses and Microarray Analysis of Gene Expression in a Multifactorial Murine Model of Age-Related Retinal Degeneration

摘要

Age-related macular degeneration (AMD) is a late-onset neurodegenerative retinal eye disease that manifests as progressive loss of central vision. It is a common disease caused by the interaction of genetic predisposition and exposure to modifiable risk factors. Risk factors identified to date include but are not limited to: advanced age, environmental factors (e.g. smoking, diet) (Chua et al. 2006; Guymer and Chong 2006; Seddon et al. 2006; Weale 2006) and genetics (e.g. complement factors H & B, LOC387715, and apolipoprotein E [APOE}) (Klaver et al. 1998; Souied et al. 1998; Schmidt et al. 2002; Edwards Iii et al. 2005; Hageman et al. 2005; Haines et al. 2005; Klein et al. 2005; Conley et al. 2006; Gold et al. 2006). We developed a murine model that closely approximates changes seen in human AMD, by combining advanced age, human APOE isoform and a high fat, cholesterol-rich (HF-C) diet, three risk factors associated with the human disease (Malek et al. 2005). We determined that aged APOE4 mice fed a HF-C diet develop characteristic lesions of AMD including retinal pigment epithelial (RPE)-pigmentary changes, thick lipid-rich diffuse and focal basal deposits and growth factor immunopositive neovascular lesions. These changes were not detected in any of the control, human APOE3 expressing mice regardless of diet consumed, nor were there any pathologies detected in young APOE4 animals.