Comparative Quantification Of Lipofuscin Deposits In the ABCA4 Knock Out Mouse Model Of STGD1 Utilizing Fluorescence Confocal Scanning Laser Ophthalmoscopy And Fourier Domain Optical Coherence Tomography

Abstract

 

Purpose:

 

To comparatively quantify the accumulation of lipofuscin in the retinal pigmented epithelium of the ABCA4 knockout (KO) mouse.

 

Methods:

 

Fluorescent intensity measurements were performed on ABCA4 mice, KO (-/-), heterozygous (+/-), and a wild type control (+/+). Lipofuscin accumulation was measured using a custom made fluorescence confocal Scanning Laser Ophthalmoscope (f/cSLO) with a 532nm excitation beam. The relative fundus autofluorescence measured from the three mice was quantitatively compared. Structural changes corresponding to retinal degeneration were quantified by measuring the thickness of the Outer Nuclear Layer (ONL) using a custom Fourier Domain Optical Coherence Tomography (FDOCT) system.

 

Results:

 

Fluorescent intensities for the two ABCA4 mice (-/- and +/-) were acquired from temporal, superior, inferior and nasal quadrants of the retina using the optic nerve head as a landmark. The +/+ rodent was utilized as a control model of normal lipofuscin accumulation.Normalized intensity data was compared at each time point. The relative accumulation of the lipofuscin in the ABCA4 -/- mouse was higher than the control as shown in the representative data in figure 1. The non-invasive measurements will be compared to histology at the experimental endpoint.

 

Conclusions:

 

Comparative in-vivo quantification of lipofuscin accumulation provides an alternative to histological tissue imaging for monitoring disease progression in the mouse model of STGD1. This baseline study validates our capacity to monitor lipofuscin accumulation and ONL structural changes non-invasively. Fig.1 (top) Fundus images of the ABCA4 KO and control mice acquired with the custom f/cSLO. (bottom) Corresponding fundus autofluorescence images indicating higher lipofuscin accumulation in the ABCA4 KO mouse.  

 

Keywords: ipofuscin • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • retinal degenerations: hereditary