Fig. 9: PIEZO1 activator YODA1 is sufficient to induce photoreceptor extrusion, but single HBEGF or TNF is not.

a Experimental design: starting from day 200, HROs were treated with PIEZO1-channel activator YODA1 (Y) alone, or in combination with either HBEGF (H) or TNF (T). In addition, HROs were also treated with HBEGF or TNF alone, or in combination (HT). (−)-Blebbistatin (BLEB, B), an inhibitor of myosin II, was applied to some HT-treated HROs starting 12 h before HT application, and then throughout the HT treatment period. HROs were analyzed at D210. b Representative ROI images recorded from immunostained serial HRO sections and quantitatively analyzed to determine the effect of the treatments, including retinal cell-type composition, pathologic changes of photoreceptor inner segments (PIS), cell death (TUNEL), glial proliferation, gliosis (GFAP), and MG delamination (see Supplementary Fig. 18c). c Schematic summary of the effects of the treatments on HROs: treatments induced either none (–), a minor ((+)), or a major (+) phenotype, or a reduction (arrows) in phenotype severity compared to HT. d Graphical depiction of statistical analysis of quantitative data shown in (b). Dark-gray squares depict significant changes (P < 0.01, one-way ANOVA with Tukey’s post hoc test) compared to control (CTRL) or HT-treated HROs, respectively. c Graphs: each circle represents 1 individual HRO (n) derived from N = 3 independent experiments (n ≥ 5/N). c Graphs (mean ± SD) and (d) statistics over n. Types of treatments are indicated (+). Scale bars: b 50 μm. See Supplementary Data 6. Source data are provided as a Source Data file.