Abstract
Purpose :
Apolipoprotein B100 (ApoB) is the main apolipoprotein of plasma low-density lipoproteins and is present in sub-RPE deposits and pro-atherogenic plaques, hallmarks of early-AMD and cardiovascular disease, respectively. Herein, we characterized the retina of transgenic mice predominantly expressing apoB100 as a model system to identify relevant endpoints for studies involving evaluation of potential therapies for retinal degenerations.
Methods :
Retinal structure and morphology of 8-10 month old male and female apoB100 (n=6) and B6/129 wildtype (WT; n=4) mice were evaluated in fundus, optical coherence tomography (OCT) and fluorescein angiography images. Electroretinograms were recorded followed by analysis of a-, b-, and c-wave amplitudes (n=6/group). Retinal and choroidal morphologies were assessed in toluidine blue stained 1μm sections. RPE-choroid ultrastructure (n=4/group) was examined by transmission electron microscopy. Retinal cryosections were stained for rhodopsin, R/G opsin, CRALBP, GFAP, PKCα, apoE, E06, calretinin to assess retinal phenotype and oil red o, bodipy and filipin to assess presence of lipids.
Results :
In vivo imaging revealed outer retinal lesions in 5/6 apoB100 mice. No lesions were seen in WT mice. Ex vivo, no genotype differences were seen in staining intensity and localization of rhodopsin, R/G opsin or other retinal markers. The most significant changes observed were in the distribution of apoE and bodipy staining, which was increased within Bruch’s membrane (BrM) of the apoB100 vs WT mice. A significant decrease in scotopic and phototopic b-wave amplitudes (24-37%, 0.005-500 cd.s/m2; 25-43%, 2-2000 cd.s/m2) was seen in the apoB100 mice. The decline in scotopic b-wave amplitude was consistent with a 23% decrease in the thickness of PKCα positive rod-bipolar cell layer.
Conclusions :
Middle age apoB100 mice demonstrate a decrease in retinal function as well as an accumulation of lipids within regions of their BrM. ApoB100 mice may be an appropriate platform to test drugs which are intended to target removal of lipids from BrM with endpoints including evaluating apoE and bodipy staining patterns, visual function as well as distribution and localization of PKCα.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.