Fig. 3

Inhibition of differentially expressed Ca²⁺-channels in rd1 retina either promote or reduce photoreceptor cell death. A Balloon plot showing time-dependent whole-retina expression changes (post-natal day (P) 7 to P21) of cyclic nucleotide-gated channel (CNGC), Ca²⁺-release activated channel (CRAC), Na⁺/Ca²⁺ exchanger (NCX), and voltage-gated Ca²⁺ channel (VGCC). B Deviation plot highlighting expression changes for CNGC, CRAC, NCX, and VGCC in P13 rd1 whole retina. C Balloon plot showing scRNA-seq data and time-dependent expression changes (post-natal day (P) 11 to P17) of CNGC, CRAC, NCX, and VGCC in rd1 rod photoreceptors. D Deviation plot highlighting expression changes for CNGC, CRAC, NCX, and VGCC in P13 rd1 rod photoreceptors. E TUNEL assay labelling dying cells (magenta) in rd1 and wild-type (wt) retinal explant cultures. DAPI (grey) was used as a nuclear counterstain. Untreated (Untr.) wt and rd1 retina were compared to retina treated with 50 µM CNGC inhibitor (L-cis diltiazem), 20 µM CRAC inhibitor (CM4620), 40 µM NCX inhibitor (SN-6), 100 µM L-type VGCC inhibitor (D-cis diltiazem), 10 µM T-type VGCC inhibitor (TTA-A2), and 15 µM α₂δ subunit VGCC ligand (DS5565). Scatter plot showing percent TUNEL-positive cells in outer nuclear layer (ONL). Dashed line indicates rd1 untr. situation, data points below this threshold indicate protective effects, data points above suggest destructive effects. Statistical testing: one-way ANOVA and Tukey’s multiple comparison post hoc test. Untr. wt: n = 5; Untr. rd1: 18; L-cis rd1: 6; CM4620 rd1: 15; SN-6 rd1: 9; D-cis rd1: 12; TTA-A2 rd1: 6; DS5565 rd1: 6; error bars represent SD; significance levels: *** = p < 0.001; **** = p < 0.0001. INL = inner nuclear layer, GCL = ganglion cell layer; scale bar = 50 µm