Abstract
Purpose: :
Dysregulation of cholesterol homeostasis is suspected to be a key factor for the development of age–related maculopathy. In the present work, we aimed to evaluate the retinal phenotype of apoB100,LDLR–/– mice, a relevant animal model for lipid metabolism dysfunction.
Methods: :
ApoB100,LDLR–/– mice were studied by standard scotopic and photopic electroretinography by comparison to control animals. Fundus images were obtained with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph). The integrity of the vascular system was investigated by means of fluoresceine and indocyanine green angiography. Sections of eye cups were stained by filipin to detect cholesterol deposits.
Results: :
Both scotopic and photopic b–wave amplitudes were reduced in apoB100,LDLR–/– mice compared to control mice after 14 months of age (38 µV vs 90 µV for the scotopic b–wave amplitude at 10 mcds/m², and 83 µV vs 161 µV for the scotopic b–wave amplitude at 25 cds/m²). Although the retinal and the choroidal vascular systems were normal, apoB100,LDLR–/– mice displayed white auto–fluorescent dots in the retinal pigment epithelium layer which likely corresponded to cholesterol deposits.
Conclusions: :
ApoB100,LDLR–/– mouse is known to be a relevant model for cardiovascular diseases. Based on our findings, we demonstrate for the first time that it displays also retinal dysfunction that may likely be due to cholesterol deposits within the retina. These data strongly support the notion that lipid dysfunction is a key feature for age–related maculopathy and suggest that apoB100,LDLR–/– is a valuable model for this disease.
Keywords: age-related macular degeneration • lipids • transgenics/knock-outs