Figure 5.

i.c.v. delivery of scAAV9.CB.CLN6 preserves photoreceptors in Cln6^nclf mice

Retinal sections through the optic nerve head stained with cresyl violet show retinal lamination and photoreceptors. (A–C) A single, postnatal day 1 injection of scAAV9.CB.CLN6 delivered via CSF largely prevents progressive photoreceptor loss in (A) 3 month, (B) 6 month, and (C) 9 month Cln6^nclf mice (ONL, arrows). As observed from representative images, wild-type animals show 10–12 rows of photoreceptor nuclei, while untreated Cln6^nclf mice retain only one layer of photoreceptors by 9 months of age. In contrast, AAV9-treated Cln6^nclf mice maintain 7–8 rows of photoreceptors at all time points examined. (D and E) Quantification of photoreceptor density at different time points is presented in (D), and quantification of photoreceptor density in different retinal areas at 9 months of age is presented in (E). (F) Lastly, retinal montage images through the optic nerve head show severe photoreceptor loss across the whole retina in untreated Cln6^nclf mice at 9 months of age (arrows), while AAV9 treatment substantially preserves photoreceptors across the central retina at the same age (arrows). Peripheral photoreceptors in treated Cln6^nclf mice are not preserved at 9 months of age (arrow). Abbreviations: RGC, retinal ganglion cells; INL, inner nuclear layer; ONL, outer nuclear layer; RPE, retinal pigment epithelium. n = 6/treatment for each time point, represented by equal numbers of males and females. Mean ± SEM, two-way ANOVA, Tukey correction. ∗∗∗∗p < 0.0001.