Fig. 7: AAV-mediated in vivo CRISPR KD of HRH1 in RGCs significantly protects RGCs and ONs and preserves visual function in two optic neuropathy models.

a Schematic illustration of the timelines of AAV injection and evaluation of neuroprotection in two optic neuropathy models. b Representative OCT images of mouse retina in at 14dpc. GCC is indicated as double end red arrows. c Quantification of GCC thickness measured by OCT at 14dpc. AAV-CL, n = 7 mice; HRH1-KD, n = 5 mice. d Upper panel: representative confocal images of the wholemount retinas; Lower panel: representative light microscope images of semi-thin transverse sections of ON with PPD staining at 14dpc. e Quantification of surviving RGC somata in wholemount retinas and axons in ON sections at 14dpc. n = 10 mice for AAV-CL, Amo; n = 5 mice for HRH1-KD. f Representative OCT images of mouse retina in living mice with SOHU glaucoma at 3wpi. GCC is indicated as double end red arrows. g Quantification of GCC thickness measured by OCT at 3wpi. n = 9 mice. h Representative confocal images of the whole retina and enlarged peripheral retina showing surviving RBPMS + (red) RGCs at 3wpi; and representative light microscope images of semi-thin transverse sections of ON with PPD staining. i Quantification of surviving RGC somata in wholemount retinas and axons in ON sections at 3wpi, represented as percentage of SOHU eyes compared to the sham contralateral control eyes. n = 9. j Visual acuity measured by OKR at 3wpi. n = 9 mice. k Left: representative wave forms of PERG at baseline and 3wpi. Right: quantification of P1-N2 amplitude of PERG at 3wpi. n = 9 mice. All data in this figure are presented as means ± s.e.m., **P < 0.01, ***P < 0.001, ****P < 0.0001, with a two-tailed unpaired Student t-test. Source data are provided as a Source data file.