A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer’s disease

Abstract

Abstract Background A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer’s disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age. Methods Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12 months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12 months of age using the novel object recognition test. Amyloid beta (Aβ) distribution in the hippocampus and the retina were visualised at 3, 6 and 12 months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups. Results Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3 months (p < 0.001). There was also a significant difference in the amplitude of pSTR between the two groups starting from 6 months (p < 0.001). Furthermore, a significant difference in the inner retinal thickness, between the two groups, was observed starting from 9 months (p < 0.001). Conclusions We observed an age-related decline in retinal functional and structural parameters in both APP/PS1 and WT controls, however, inter-group analysis revealed that inner retinal functional and structural decline is exacerbated in APP/PS1 mice, and that retinal functional changes precede structural changes in this strain. Further studies are required to confirm whether such phenomenon occurs in humans and if studying retinal functional changes can aid-in early assessment of AD.

Keywords

• Retinal function
• Retinal structure
• Retinal imaging
• Biomarkers
• Alzheimer’s disease
• Early assessment