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

Abstract

Animal models of disease are paramount to understand retinal development, the pathophysiology of eye diseases, and to study neurodegeneration using optical coherence tomography (OCT) data. In this study, we present a comprehensive normative database of retinal thickness in C57BL6/129S mice using spectral-domain OCT data. The database covers a longitudinal period of 16 months, from 1 to 16 months of age, and provides valuable insights into retinal development and changes over time. Our findings reveal that total retinal thickness decreases with age, while the thickness of individual retinal layers and layer aggregates changes in different ways. For example, the outer plexiform layer (OPL), photoreceptor inner segments (ILS), and retinal pigment epithelium (RPE) thickened over time, whereas other retinal layers and layer aggregates became thinner. Additionally, we compare the retinal thickness of wild-type (WT) mice with an animal model of Alzheimer's disease (3 × Tg-AD) and show that the transgenic mice exhibit a decrease in total retinal thickness compared to age-matched WT mice, with statistically significant differences observed at all evaluated ages. This normative database of retinal thickness in mice will serve as a reference for future studies on retinal changes in neurodegenerative and eye diseases and will further our understanding of the pathophysiology of these conditions.

Keywords: 3 × Tg-AD animal model; Alzheimer's disease; normative data; optical coherence tomography; retinal thickness.

Figure 1

Representative B-scan with overlayed segmentation. RNFL-GCL, retinal nerve fiber layer and ganglion cell layer complex; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ILS, photoreceptor inner segments; OLS, photoreceptor outer segments; RPE, retinal pigment epithelium; TRT, total retina thickness.

Figure 2

Average total retinal thickness maps of wild-type (WT) and the triple transgenic mouse model of Alzheimer's disease (3 × Tg-AD) retinas separated by left (OS) and right (OD) eyes of animals aged 1, 4, 8, 12, and 16 months. Color represents the retinal thickness in μm as indicated by the color bar. S, superior; I, inferior; T, temporal; N, nasal.

Figure 3

Kernel density estimates of the total retinal thickness (TRT) for the left eye (OS) and right eye (OD) of wild-type (blue) and the triple transgenic Alzheimer's disease (3xTg-AD) mice (red). Median (dashed) and first and third quartiles (dotted) are shown. p-values < 0.01 (■) and < 0.001 (*).

Figure 4

Kernel density estimates of retinal thickness per layer for the left (A) and right (B) eyes of wild-type (blue) and the triple transgenic Alzheimer's disease (3xTg-AD) mice (red). Median (dashed) and first and third quartiles (dotted) are shown. Bonferroni correction was applied per time point to correct for multiple comparisons. p-values < 0.05 (•), < 0.01 (■), and < 0.001 (*). RNFL-GCL, retinal nerve fiber layer and ganglion cell layer complex; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ILS, photoreceptor inner segments; OLS, photoreceptor outer segments; RPE, retinal pigment epithelium.

Figure 5

Longitudinal total retinal thickness of wild-type (A, B) and the triple transgenic Alzheimer's disease (C, D) mice for left (OS; blue) and right (OD; red) eyes. Color coded p-values for pairwise comparisons are shown in (B) and (D). The color indicates the level of the p-value, as indicated by the color bars. p-values < 0.05 (•), < 0.01 (■), and < 0.001 (*).

Figure 6

Normalized longitudinal mean retinal thickness variations for wild-type mice, differentiated by layer and block (B1–B9). Data were normalized for each retinal layer/layer aggregates. Normalized thickness is indicated by the color bar. RNFL-GCL, retinal nerve fiber layer and ganglion cell layer complex; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ILS, photoreceptor inner segments; OLS, photoreceptor outer segments; RPE, retinal pigment epithelium; TRT, total retina thickness.