Fig. 5: Genetic autophagy inhibition curtails the visual defect of an ADOA mouse model.
From: Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
a Average ± SEM visual acuity of 4-month-old mice of the indicated genotype in the optokinetic test. Mice were subjected to visual stimuli at the indicated temporal and spatial frequencies. Visual acuity is proportional to the percentage of correct answers to the stimulus. WT, n = 10; Opa1ΔRGC/ΔRGC, n = 10; Opa1ΔRGC/ΔRGCAtg7ΔRGC/+, n = 8 mice. ****p < 0.0001 vs. WT in two-way ANOVA/Tukey’s test. b A schematic of the Y-shaped pool used for the vision guided forced-swimming test. The two screens (gray and vertically striped) used as visual cues and the submerged platform are shown. c Average ± SEM visual acuity of 4-month-old mice of the indicated genotype in the vision guided forced-swimming test. WT, n = 9; Opa1ΔRGC/ΔRGC, n = 5; Opa1ΔRGC/ΔRGCAtg7ΔRGC/+, n = 7 mice. *p = 0.05, ***p = 0.0001 vs. WT in two-way ANOVA/Tukey test. d Representative z-projections of stacks of confocal images of the fluorescence of OPA1 (red), LC3B (green), and DAPI (blue) of retinal slices of 4-month-old mice of the indicated genotype. The soma of RGCs are circled with white lines in right panels. Bars, 20 μm. GCL ganglion cell layer, IPL inner plexiform layer, INL inner nuclear layer. e Quantification of RGCs autophagosomes number in three independent experiments as in (d). WT, n = 163; Opa1ΔRGC/ΔRGC, n = 155; Opa1ΔRGC/ΔRGCAtg7ΔRGC/+, n = 156 cells. ***p = 0.0002 vs. WT in one-way ANOVA/Bonferroni’s test. f Quantification of mitochondria and autophagosomes accumulation in axonal hillocks of RGCs in three independent experiments as in (d). For mitochondria, WT, n = 165; Opa1ΔRGC/ΔRGC, n = 155; Opa1ΔRGC/ΔRGCAtg7ΔRGC/+, n = 156; for autophagosomes, WT, n = 164; Opa1ΔRGC/ΔRGC, n = 155; Opa1ΔRGC/ΔRGCAtg7ΔRGC/+, n = 155 cells. **p = 0.003 ***p = 0.001 vs. WT in one-way ANOVA/Tukey’s test. g Quantification of anti-LC3B antibody signal in sorted mtYFP+ RGCs from five animals of each indicated genotype. *p = 0.012 vs. WT in one-way ANOVA/Kruskal–Walli’s test. In box plots, centre line represents mean, bounds of boxes SEM, whiskers the 10th–90th percentiles; each dot represents an individual nematode form the indicated N of independent experiments. Source data are provided as a Source Data file.
