Fig. 1

dBET6 degrades BET proteins in mouse retina and in 661W cells. A Diagrams show the chemical structure (left) and working model (right) of dBET6 to degrade BET proteins. B WES and WB analysis show degradation of BRD2, 3, and 4 in mouse retina after i.p. injection of dBET6 (10 mg/kg). Total retinal proteins were extracted at the indicated time points post-injection. WES did not give clear band for BRD4, thus traditional WB analysis was conducted for BRD4 detection. Right panels show quantification results. ns not significant; *p < 0.05; **p < 0.01; ***p < 0.0005, n = 3 eyes per group, One-way ANOVA, Tukey’s test. C, D Mice received two i.p. injections of dBET6 (10 mg/kg) with a 24 h interval. Analysis was conducted 8 days after the second injection. C In vivo OCT shows retina structure and heat map shows the retina thickness. The lower panels show average retinal thickness in the 3 mm and 6 mm circles. ns not significant, n = 5 mice for vehicle and n = 7 mice for dBET6 group, respectively. ILM internal limiting membrane, INL inner nuclear layer, ONL outer nuclear layer, BM Bruch’s membrane. D Representative HE staining shows retina morphology. Scale bar: 500 μm for the upper panels and 50 μm for the enlarged lower panels. n = 3 eyes per group. GCL ganglion cell layer, IPL inner plexiform layer, OPL outer plexiform layer, RPE retinal pigment epithelium. E Representative dark-adapted ERG recording. Mice received two injections of vehicle or dBET6 with a 24 h interval. Analysis was conducted 1 day (1D) or 8 days (8D) after the second injection. Right panels show luminance-response results for the a- and b-waves from mice of indicated treatment. n = 5 mice, 8–10 eyes per group, ns: not significant, Two-way ANOVA, Tukey’s test. F WB analysis show degradation of BRD4 by dBET6 treatment (2 h) in the photoreceptor-like cells 661W. G 661W cells were treated with DMSO or dBET6 (100 nM) for 2 h, or pretreated with MG132 (50 μM) for 2 h and then dBET6 (100 nM) was added for additional 2 h before collection for WB analysis. Right panel shows the quantification result of WB. ns not significant, **p < 0.01; n = 3 per group, one-way ANOVA, Tukey’s test