Fig. 1
Progressive vision loss and neuronal dysfunction yet no overt retinal neurodegeneration in Wfs1 knockout mice. a, b Visual function is affected in Wfs1 KO compared to WT mice, with contrast sensitivity (a) being affected earlier in life than visual acuity (b). Two-way ANOVA with Sidak’s multiple comparisons; F1,80=65.04 and p < 0.0001 for genotype, F3,80=90.47 and p < 0.0001 for age, for contrast sensitivity; F1,48=40.33 and p < 0.0001 for genotype, F3,48=5.524 and p = 0.0024 for age, for visual acuity. c The amplitude of the positive scotopic threshold response is reduced in Wfs1 KO mice. Mixed-effects analysis with Sidak’s multiple comparisons; F1,15=18.46 and p = 0.006 for genotype, F3,31=1.006 for age. d Latency of visual evoked potentials increases with age in Wfs1 KO compared to WT mice. Two-way ANOVA with Sidak’s multiple comparisons; F1,80=24.90 and p < 0.0001 for genotype, F3,80=6.720 and p = 0.0004 for age. e Representative CAP traces for wild type and Wfs1 KO mice and the conduction velocity of the individual peaks at baseline (0.4 Hz). f, g Relative changes in peak amplitude, in response to increasing stimulation frequencies, show a larger CAP peak amplitude (P2) drop at 50 Hz in Wfs1 KO nerves compared to WT (g). Unpaired t-test; t8 = 2.317 and p = 0.0492. h-i Mn2+−enhanced MRI of the retinocollicular projection reveals a reduced optic nerve diameter (h) and superior colliculus innervation (i). Two-way ANOVA with Sidak’s multiple comparisons; F1,74=21.41 and p < 0.0001 for genotype, F3,74=3.588 and p = 0.0178 for age, for optic nerve; F1,60=142.6 and p < 0.0001 for genotype, F3,60=3.331 and p = 0.0253 for age, for superior colliculus. j Analysis of the thickness of the retinal layers, as measured by optical coherence tomography, shows no differences between Wfs1 KO and WT mice at 7.5 months of age. Multiple unpaired t-tests: t9 = 0,3632 for neuroretina, t9 = 1,587 for NFL + GCL, t9 = 1,137 for IPL, t9 = 1,962 for INL, t9 = 1,932 for OPL, t9 = 0,07964 for ONL, t9 = 0,9323 for PRL. k, l Cell counts of retinal ganglion cells (k) and dopaminergic amacrine cells (l) reveal similar numbers in 7.5-month-old Wfs1 KO and WT animals. Unpaired t-test; t15 = 20.8088 for ganglion cells; t7 = 0.2544 for amacrine cells. Data presented as mean ± SEM, number of animals (N) depicted in the bar graphs