Fig. 6. Targeting actin severing pathways rescues shedding of vesicles from Rpgr-mutant photoreceptors.

a TEM reveals high numbers of vesicles shed from OS bases in Rpgr^Ex3d8 photoreceptors (middle panel) compared to controls (left panel). Shedding of vesicles is reduced upon intravitreal delivery of 25 mM cytochalasin D for 6 h (right panel) (OS = Outer Segment; cyan * = OS base). b Quantification of vesicle shedding at the base of photoreceptors by TEM. (Black symbols = mean number of vesicles at the base of each photoreceptor per experimental animal; N = 3 animals per genotype; error bars represent standard error of the mean; **p = 0.0068, *p = 0.0108; two-tailed, unpaired t-test; error bars denote SEM. Different colours represent measurements from individual mice). c TEM reveals intravitreal delivery of 100 μM LIM kinase inhibitor for 6 h to wild-type retinas leads to elongation of basal discs (blue arrows, left panel). Intravitreal LIMKi delivery to Rpgr^Ex3d8 eyes reduces number of OS shed vesicles (middle and right panels; cyan * = OS base). d Quantification of vesicle shedding by control or LIMKi treatment from TEM images. (Black symbols = mean number of vesicles at OS base of photoreceptors per experimental animal; N = 3 animals per genotype; error bars represent standard error of the mean; ****p ≤ 0.0001; two-tailed, unpaired t-test; error bars denote SEM. Different colours represent measurements from individual mice). (Scale bars; a = 1 µm; c = 500 nm for 4 left panels of wild type treated photoreceptors; 1 µm for middle and right Rpgr^Ex3d8 panels). Source data are provided as a Source Data file.