Figure 5. The HDACi's sodium butyrate (NaBu) and CI-994 reproduce the effects of VPA. A, Venn diagram showing overlapping pharmacological activities of compounds examined. B, Effect of NaBu on total rod opsin levels. NaBu ameliorates RD in P23H X. laevis in a dose-dependent manner (ANOVA, p = 0.0022). Treatment with 300 μm sodium butyrate is equivalent to dark rearing. WT animals are unaffected (ANOVA, p = 0.10). p-values shown are Dunnet's multiple comparisons. n = 7–10 animals per group. C, Representative cryosections of contralateral eyes confirm that effects of NaBu in dot blot assays are due to reduced RD in P23H-transgenic animals. OSs were stained with WGA (green) and Hoechst dye (blue). NaBu treatment resulted in greater density of OSs in P23H X. laevis. WT animals were unaffected. D, Dot blot analysis of total rod opsin from whole-eye extracts of P23H X. laevis treated with varying concentrations of CI-994. CI-994 increased total rhodopsin significantly and in a dose-dependent manner (ANOVA, p = 4.5 × 10−13). p-values shown on chart are Dunnet's multiple comparisons. n = 7–10 animals per group. E, Representative cryosections of contralateral eyes confirm that effects of CI-994 in dot blot assays are due to reduced RD in P23H-transgenic animals. OSs were stained with WGA (green) and Hoechst dye (blue). CI-994 treatment resulted in greater density of OSs in P23H X. laevis. Scale bar, 50 um. F–K, Same as described in Figure 2, A–C. F–H, Effects of NaBu on light-exacerbated RD in P23H animals were identical to the effects of VPA (two-way ANOVA, cyclic light: pg = 3.7 × 10−15, pt = 1.6 × 10−9, pi = 4.3 × 10−6. Two-way ANOVA, dark: pg = 0.03, pt = 0.005, pi = 0.11), n = 5–14 animals per group. I–K, Effects of CI-994 on light-exacerbated RD were essentially identical to the effects of VPA (two-way ANOVA, cyclic light: pg = 1.9 × 10−7, pt = 0.038, pi = 5.0 × 10−6; two-way ANOVA, dark: pg = 2.2 × 10−10, pt = 1.6 × 10−10, pi = 0.036.). N = 8–12 animals per group. Error bars indicate SEM.
Image published in: Vent-Schmidt RYJ et al. (2017)
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