Retinal Thickness Changes Over Time in a Murine AD Model APPNL-F/NL-F

Abstract

Background: Alzheimer's disease (AD) may present retinal changes before brain pathology, suggesting the retina as an accessible biomarker of AD. The present work is a diachronic study using spectral domain optical coherence tomography (SD-OCT) to determine the total retinal thickness and retinal nerve fiber layer (RNFL) thickness in an APPNL−F/NL−F mouse model of AD at 6, 9, 12, 15, 17, and 20 months old compared to wild type (WT) animals.Methods: Total retinal thickness and RNFL thickness were determined. The mean total retinal thickness was analyzed following the Early Treatment Diabetic Retinopathy Study sectors. RNFL was measured in six sectors of axonal ring scans around the optic nerve.Results: In the APPNL−F/NL−F group compared to WT animals, the total retinal thickness changes observed were the following: (i) At 6-months-old, a significant thinning in the outer temporal sector was observed; (ii) at 15-months-old a significant thinning in the inner temporal and in the inner and outer inferior retinal sectors was noticed; (iii) at 17-months-old, a significant thickening in the inferior and nasal sectors was found in both inner and outer rings; and (iv) at 20-months-old, a significant thinning in the inner ring of nasal, temporal, and inferior retina and in the outer ring of superior and temporal retina was seen. In RNFL thickness, there was significant thinning in the global analysis and in nasal and inner-temporal sectors at 6 months old. Thinning was also found in the supero-temporal and nasal sectors and global value at 20 months old.Conclusions: In the APPNL−F/NL−F AD model, the retinal thickness showed thinning, possibly produced by neurodegeneration alternating with thickening caused by deposits and neuroinflammation in some areas of the retina. These changes over time are similar to those observed in the human retina and could be a biomarker for AD. The APPNL−F/NL−F AD model may help us better understand the different retinal changes during the progression of AD.

The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer’s disease: an exploratory analysis

“…However, in our work, no statistically significant brain changes were observed between participants with FH+ ApoE ɛ4+ and FH− ApoE ɛ4−. This result is supported by previous studies that showed that retinal changes appear earlier than brain changes [ 13 , 37 – 39 ]. Also, these retinal alterations, which could occur through retrograde transneuronal neurodegeneration [ 40 ], may be associated with atrophic brain changes already present before the appearance of clinical cognitive symptoms [ 17 , 41 ].…”

Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease

“…At all ages studied, we found that the retina of 3×Tg-AD mice was thinner than that of age-matched WT mice. This is consistent with findings reported in the literature for animal models of AD (Chiquita et al, 2019a;Salobrar-García et al, 2021) and human patients (Marziani et al, 2013).…”

“…Mouse models have been important in multiple areas of research and have improved our understanding of disease pathophysiology. Based on OCT imaging, retinal changes induced by neurodegenerative diseases have been found, including changes in retinal layer thickness (Cunha et al, 2016 ; Song et al, 2020 ; Salobrar-García et al, 2021 ). Recently, we have also shown that retinal texture biomarkers can help discriminate between age-matched healthy controls and animal models of Alzheimer's disease (AD) in the early stages (Nunes et al, 2019 ; Ferreira et al, 2020 , 2022 ; Guimarães et al, 2022 ).…”

Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis

“…This could explain the possible alterations found in both the retina and choroid of subjects at high genetic risk of developing AD, who are also part of this study, and which we have reported in a previous work [ 21 , 30 ]. We have also demonstrated these alterations in the retina of a murine model of preclinical AD [ 37 ]. All these findings support the idea that the changes produced by AD may appear early in the retina, even before the onset of brain alterations [ 38 ].…”