Fig. 6: Partial rescue of retinal degeneration is observed following RNA replacement gene therapy in the rapidly degenerating Nrl.GFP/+, Rho^P23H/+ mouse model of ADRP.

a Effect of subretinal injection of 2 × 10⁸gc AAV-M3.M5^H.RHO^M3/5R on PRL thickness (mean ± SEM; n = 17). Two way ANOVA for effect of injection F(1, 15) = 6.999; p = 0.018; *p = 0.018, ***p = 0.0006, ****p < 0.0001, Šidák’s multiple comparisons test. b Representative SD-OCT images of right (treated) and left (untreated) eyes of a single animal taken one month following superior subretinal injection of 2 × 10⁸gc AAV-M3.M5^H.RHO^M3/5R. Orientation of sections is indicated by white arrows on corresponding en face infrared images shown to the left. Magnified views of equivalent points of temporal retina are shown in which the thickness of surviving PRL is highlighted by yellow arrows. c En face cSLO fluorescence imaging of Nrl.GFP/+, Rho^P23H/+ retinas following subretinal injection of 2 × 10⁸gc AAV-M3.M5^H.RHO^M3/5R or PBS (sham). Representative blue autofluorescence (BAF) images and BAF mean grey value (BAF^mGV) surface plots taken 4 weeks post-treatment. Red signal represents increased density of surviving rods³⁶. Paired right (injected) and left (uninjected) eyes are shown in each case. d Dark-adapted a- and b-wave and light-adapted ERG responses recorded 3 months after uniocular sham (PBS) injection (mean ± SEM; n = 14). a-wave measurements were recorded with flash intensity 10 cd.s/m² whilst b-wave responses followed dim flashes of 0.0001 cd.s/m². **p = 0.0039, ***p = 0.0005, ****p < 0.0001, Šidák’s multiple comparisons test. e Equivalent ERG responses recorded three months after uniocular treatment with 2 × 10⁸gc AAV-M3.M5^H.RHO^M3/5R (mean ± SEM; n = 17). f ERG signal of treated eyes normalised to that of fellow untreated eyes at 1-, 3- and 6-months post-injection (mean ± SEM; n = 17, 7 and 14 for AAV-M3.M5^H.RHO^M3/5R, AAV-RHO and Sham groups respectively). One month **p = 0.0073; 3 months dark-adapted a-wave *p = 0.0414, light-adapted response *p = 0.012, Šidák’s multiple comparisons test.