Fig. 7

Anterograde transport impairment in 3xTg RGCs precedes neuronal death. a-f Unbiased stereological rostral to caudal sampling of the superior colliculus after CTβ injection showed no changes in CTβ labeling in 21-day-old wild-type or 3xTg mice. In contrast, a marked reduction of CTβ labeling was observed in both 3- and 6-month-old 3xTg mice relative to controls. g Quantification of the total CTβ-positive region in the superior colliculus demonstrated a striking loss of anterograde transport in transgenic mice compared to age-matched wild-type (WT) controls (3-month-old 3xTg: n = 5, 3-month-old WT: n = 3, 6-month-old 3xTg: n = 5, 6-month-old WT: n = 5, Student’s t-test, * = p < 0.05). h, i Co-labeling of CTβ (green) with the RGC-specific marker Brn3a (red) confirmed effective CTβ uptake by RGCs in both 3xTg and WT retinas. j Quantitative analysis confirmed that there was no difference in the number of CTβ- and Brn3a-positive RGCs between 3xTg and WT retina at 3 or 6 months of age (3-month-old 3xTg: n = 3, 3-month-old WT: n = 3, 6-month-old 3xTg: n = 3, 6-month-old WT: n = 4). k-m Flat-mounted retinas labeled with the RGC-specific marker RBPMS were used to quantify RGC density (survival). o Quantitative analysis of RGC density demonstrated absence of cell death in 3-month-old 3xTg mice, while only a modest loss was observed in 6-month-old transgenic animals relative to age-matched WT controls (3-month-old 3xTg: n = 5, 3-month-old WT: n = 6, 6-month-old 3xTg: n = 5, 6-month-old WT: n = 5, Student’s t-test, *p < 0.05, n.s.: not significant p > 0.05). Scale bars: A-D = 500 μm, F-G = 25 μm, K-N = 7.5 μm