Fig. 7: TMB administration stabilizes retinal transcriptome and improves visual function in Rpe65−/− mice. | Nature Communications

Fig. 7: TMB administration stabilizes retinal transcriptome and improves visual function in Rpe65−/− mice.

From: A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models

Fig. 7

A Study design. B Group-averaged scotopic ERGs. Thin lines represent responses from individual mice. C Scotopic ERG a- and b-wave amplitudes. D–I Ex vivo ERG. The perfusion medium was supplemented with synaptic blockers (vehicle, n = 6; TMB, n = 7 mice), or not (vehicle, n = 6; TMB, n = 6 mice). H–I Averaged intensity-response functions for ERG a-wave H or b-wave I recorded in the presence or absence of synaptic blockers, respectively. J Optomotor responses at different pattern contrasts. K Outer retina thickness as measured from OCT images. L Whole dorsal retina M-cone counts from retinal whole mounts. M Venn diagram of differentially expressed genes in retinal bulk RNA-seq. Comparison shown between WT, Rpe65-/--vehicle, and Rpe65-/--TMB groups. N Expression heatmap of 10 most highly expressing mitochondrial-encoded genes. The asterisks in heatmaps indicate significant difference (adjusted for multiple comparisons) compared to expression in WT mice. O Expression heatmap of 5000 most highly expressing nuclear-encoded genes. For clarity of presentation outlier genes Gm4735 and Eno1b were removed. P, Q Volcano plots of DE genes between WT and vehicle-treated Rpe65-/- mouse MG cells P, or WT and TMB-treated Rpe65-/- mouse MG cells Q, from scRNA-seq data. Each Rpe65-/- group data was derived from cell suspensions combining seven retinas, whereas the WT group consisted of three retinas. Analysis was performed from 4,135 cells of the WT mice; 3979 cells from vehicle-treated; and 5,901 cells from TMB-treated Rpe65−/− mice. R DE gene comparison of Rpe65-/--vehicle and Rpe65-/--TMB groups in MG cells. Selected enriched KEGG pathways are shown. Data in graphs C, H, I and J were analyzed using RM two-way ANOVA with the Geisser-Greenhouse correction, whereas data in graph K were analyzed by 1-way ANOVA followed by the Bonferroni post hoc test: ****P < 0.0001. Data in graph L were analyzed by Welch´s t-test. The pound signs indicate an ANOVA-significant main effect between treatments: #P < 0.05, ####P < 0.0001. Data are presented as mean ± SD. Source data are provided as a Source Data file.

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