Figure 4

Drug screening in the RP #5 iPSC-derived rod photoreceptor cells. (A) Relative number of pNrl-EGFP-positive rod photoreceptor cells derived from #5 iPSCs after treatment with each therapeutic reagent. N = 9. (B-E) Relative mRNA levels of BiP (B), CHOP (C), BID (D), and NOXA (E) in the pNrl-EGFP-positive cells cultured with rapamycin, PP242, AICAR, NQDI-1, and salubrinal at 5 weeks after differentiation. Each reagent increased the rod photoreceptor cell survival at 5 weeks, whereas ER stress and apoptotic markers were suppressed. N = 3 for B-E. Rapa., rapamycin; Salub., salubrinal. *p < 0.05, **p < 0.01, ***p < 0.001. Mean ± SD relative to cont. (with each p-values of marked by *) for Cont., Rapa., PP242, AICAR, NQDI-1, Salbr. in (A) 1 ± 0.182, 3.02 ± 0.920, 3.49 ± 0.976, 3.67 ± 1.22, 2.99 ± 0.513, 2.19 ± 1.12 (all, p < 0.0001); (B) 1 ± 0.005, 0.654 ± 0.001, 0.990 ± 0.001, 0.932 ± 0.001, 0.989 ± 0.001, 0.714 ± 0.004 (all, p < 0.0001); (C) 1 ± 0.002, 0.608 ± 0.003, 0.842 ± 0.009, 0.802 ± 0.003, 0.830 ± 0.003, 0.733 ± 0.008 (all, p < 0.0001); (D) 1 ± 0.016, 0.681 ± 0.006, 0.954 ± 0.007, 0.864 ± 0.002, 0.934 ± 0.004, 0.816 ± 0.008 (all, p < 0.0001); (E) 1 ± 0.005, 0.671 ± 0.001, 0.760 ± 0.004, 0.743 ± 0.003, 0.816 ± 0.001, 0.849 ± 0.006 (all, p < 0.0001). These data were obtained by technical triplicate and not by biological triplicate. All statistical analyses in this figure were carried out by One-way ANOVA Dunnett’s test.