Influence of amyloid pathology on retina and dLGN in 5xFAD mouse model

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by
the formation of amyloid beta plaques and neurofibrillary tangles that
leads to decreased quality of life due to behavioral, motor, and cognitive
impairments.  Due to the widespread pathological nature of AD,
many brain regions are affected by amyloid beta plaques including regions
important for vision such as the lateral geniculate nucleus (LGN) of the
thalamus which is critical for relaying signals from the retina to the
primary visual cortex.  Using a wide range of techniques
including electrophysiological approaches, in vivo and ex vivo imaging
methods, and immunohistochemistry in a mouse model with progressing
amyloidosis (5xFAD), the goal of this study was to determine whether
AD-like pathology disrupts neuronal and synaptic structure and function in
the visual system.  In vivo electroretinogram recordings revealed
photoreceptor dysfunction in the 6- and 9-month-old 5xFAD mice, while
optical coherence tomography indicated no changes in retinal
thickness.  In the dorsolateral geniculate nucleus (dLGN), the
rodent homolog of the primate LGN, we identified decreased densities of
retinal ganglion cell axon terminals and fewer thalamocortical (TC) neuron
cell bodies.  No detectable deficits in excitatory synaptic
function or TC neuron dendritic structure were seen in the dLGN, and
reflexive visual behavior was also found to be normal in the 5xFAD
mice.  These results indicate relatively modest amyloid-triggered
dysfunction in these stages of the visual system suggesting that amyloid
beta plaque formation may play only a small role in the visual system
dysfunction seen in AD patients.  These results may also point to
potential compensatory mechanisms that preserve function of visual
pathways in the 5xFAD visual system.