Retinal microglial activation in the triple-transgenic Alzheimer’s Disease mouse model (3xTg-AD).

Abstract

Purpose : Alzheimer's disease (AD) is a neurodegeneration that constitutes the most common type of dementia in the world. The main features associated with AD are amyloid protein plaques -β (Aβ) and tau protein neurofibrillary tangles, which lead to a microglial cell-mediated neuroinflammation in the brain. The retina as a window to the brain can also be affected in AD, presenting some molecular and cellular changes such as microglial activation. The aim of the present study was to analyze microglial changes in retinal whole-mounts in the triple-transgenic AD mouse model (3xTg-AD).

Methods : Whole retinal mounts were processed with anti Iba-1 to perform a quantitative morphometric analysis of microglia activation in the 3xTg-AD mice and wild-type mice (n=8 in both group), which allows the visualization of the whole microglial cell, as well as its location along the extension of the retina in different layers. A quantification of Iba-1+ cells and of the cell body area in the outer plexiform layer and in the inner retinal layer complex, constituted by the inner plexiform layer and the nerve fiber layer-ganglion cell layer were performed.

Results : Compared to wild animals, the retina of 3xTg-AD mice shows a thicker microglial cell body area and a higher number of microglial cells. In addition, the microglial retract, migrate, and reorient their processes, changing their location from a parallel position to one that is perpendicular to the surface of the retina as well as well as forming groups in rows or circular clusters.

Conclusions : In the 3xTg-AD model, microglial cells showed several signs of activation, such as increased number and soma size, and retraction and reorientation of their processes, and changes in the cell’s location. These morphological changes could represent that in this model of AD a neuroinflammatory process is taking place.

This is a 2021 ARVO Annual Meeting abstract.