Structural, functional and molecular alterations in the retina of a mouse model of Alzheimer’s disease

Abstract

Purpose : Vision abnormalities are early complaints of Alzheimer’s disease (AD) patients. Understanding if the retina and brain share similar changes could help filling in missing gaps in AD pathology and unravel if the retina could be used as a reliable tool for AD diagnosis. Previously, we found a few functional, structural and molecular changes in the mice retina and brain of an animal model of AD, at early time points (4 and 8 months of age). In this work, we focused our attention on the potential changes in the retina and brain at a later timepoint, 12 months.

Methods : Male triple transgenic (3xTg-AD; AD model) and wild-type (WT; C57BL6/129S) mice (12 months old) were used to evaluate retinal structural and functional changes by optical coherence tomography (OCT), electroretinography (ERG; scotopic a-wave, b-wave and oscillatory potentials) and pattern ERG (PERG). Retina, hippocampus (HIP) and total cortex (CTX) regions were used to assess amyloid beta (Aβ), synaptic loss and glial reactivity.

Results : At 12 months, there was a significant reduction in total retinal thickness of 3xTg-AD mice compared with WT (181.96±0.66 μm vs 189.44±0.71 μm; p<0.05) that was more evident in ganglion cell and inner plexiform layers. No alterations were detected in the a-wave amplitude. However, the b-wave amplitude was significantly enhanced in 3xTg-AD mice comparing to WT (119.34±15.29 vs 20.25±5.62; p<0.05). The oscillatory potentials in the 3xTg-AD mice presented a faster response than WT. No changes were detected in PERG recordings. Aβ levels increased in the HIP (387.28±48.39% of WT) and CTX (195.91±24.81% of WT) of 3xTg-AD, but not in the retina. Synaptophysin and syntaxin, two synaptic proteins, and the enzyme choline acetyltransferase remained unchanged in the 3xTg-AD mice in the regions analyzed. The GFAP protein levels increased in the retina (151.40±19.68% of WT) and the HIP (290.57±45.67% of WT) of the 3xTg-AD. The protein levels of vimentin, a Müller cell marker, and its distribution did not change.

Conclusions : This study shows that at a late stage (12 months) the retinal function and structure of 3xTg-AD mice are affected. However, at this timepoint, we did not find substantial molecular and cellular changes in the retina and brain, with the exception of GFAP. Additional biomarkers and later timepoints must be analyzed to better understand this pathology.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.