A novel murine model of aging of the human retina

Abstract

Abstract Purpose Accumulation of lipids, and especially of cholesteryl esters, under the retinal pigment epithelium and within Bruch’s membrane is a normal feature of aging and has also been observed in human eyes with age‐related maculopathy. Our objective was to evaluate the retinal phenotype of apoB100,LDLR‐/‐ mice, a model for lipid metabolism dysfunction and potentially of aging of the retina. Methods ApoB100,LDLR‐/‐ mice were studied at 7 and 14 months of age by standard scotopic and photopic electroretinography by comparison to control animals. Fundus images were obtained with a confocal SLO (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 (Rmax=125 µV vs 208 µV for the scotopic b‐wave amplitude at 7 months, and 83 µV vs 162 µV at 14 months). Similarly rods and cones sensitivity was 0.5log unit lower in apoB100,LDLR‐/‐ mice at 14 months, compared to control mice. 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. Conclusion The present apoB100,LDLR‐/‐ mouse, is one of the only models with neutral lipid deposits at the basement of RPE that can potentially be very useful to study the mechanisms of lipid deposition that occurs universally in human retina while aging.