Retinal ganglion cells in a mouse model of Alzheimer's disease: A temporal study

Abstract

Aims/Purpose: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by the progressive loss of neurons and their synapses in the brain. Similar alterations have been observed in the retina even before they manifest in the brain. The retina has been proposed as a readily accessible biomarker for AD. In a previous work utilizing a murine model of AD (APPNL‐F/NL‐F), changes in retinal thickness, as measured by optical coherence tomography (OCT), were observed at 15 and 17 months. The objective of this study was to quantitatively assess the population of retinal ganglion cells (RGCs) in this same AD murine model over a specified time period and compare it with wild‐type (WT) mice.Methods: To quantitatively assess the population of retinal ganglion cells we used two study groups: the APPNL‐F/NL‐F model throughout the time period of (6, 9, 12, 17, and 20 months) and compared with wild‐type (WT) mice age matched (n = 30 in both groups). The quantification of retinal ganglion cells (RGCs) was conducted using immunohistochemical analysis with the Brn3a marker. This analysis was performed using a semi‐automatic algorithm implemented in the MatLab environment, which was developed by the Ramón Castroviejo Institute for Ophthalmic Research. For the analysis, the entire retina was considered and segmented into the peripapillary, intermediate, and peripheral zones.Results: A statistically significant decresase (p < 0.05) in the population of Brn3a + cells was observed in the APPNL‐F/NL‐F group compared to the WT group. This decreased was found in the total retina at 12 months, in the peripapillary zone at 9, 12, and 20 months, and in the intermediate zone at 12 months of the study.Conclusions: The APPNL‐F/NL‐F mouse model exhibits RGCs loss at 9, 12, and 20 months, mirroring the patterns observed in human cases. These findings suggest that the model holds promise for investigating and studying mechanisms related to RGC degeneration in Alzheimer's disease.