Fig. 2: The therapeutic efficacy of RIDE in the retinal vascular disease model.
a, Experimental workflow. b, Schematic diagram of subretinal injection. c, Deep-sequencing analysis of the on-target (On) and off-target (OT) effects of the Vegfa-targeting RIDE in RPE cells in vivo. n = 1 mouse. d, ELISA of VEGF-A levels in the RPE/choroid/scleral (RCS) complex. n = 9 mice. PBS versus RIDE, **P = 0.0023. e, Representative laser-induced CNV areas in IB4-stained choroidal flat mounts of mouse eyes injected with RIDE or PBS. The white arrowheads indicate the position of the optic disc. The dashed white circles delineate the CNV region. Scale bar, 200 μm. f, Analysis of the CNV areas in five mice 7 days after laser treatment using IB4-stained choroidal flat mounts. A total of 100 ng p24 RIDE was administered into each eye. n = 18 CNV areas, PBS versus RIDE, *P = 0.0254. g, Representative trace of the a- and b-wave amplitudes in the presence of a scotopic-adapted 3.0 Hz stimulus. h,i, Quantitative analysis of a-wave (h) and b-wave (i) (n = 5 mice). j, Visualization of the 22 identified clusters using two-dimensional tSNE. PCA of 19,079 single-cell expression profiles was obtained from the RPE layers of the PBS, RIDE and empty VLP groups (four mice from each group). A total of 100 ng p24 RIDE or VLP was injected subretinally. k, Determination and clustering of cell types according to the average expression of known marker genes for each cluster. Violin plots of gene expression are shown alongside the dendrogram. l, Cell composition distribution in the RPE tissue after different treatments. Data and error bars represent the mean ± s.e.m. Paired two-tailed Student’s t-tests for d and unpaired two-tailed Student’s t-tests for f. Two-way ANOVAs for h and i.
