Figure 5.

Ultrastructural analysis of combined suppression and replacement-treated retinas 20 weeks postinjection. The right eyes of P5 P347S mice were subretinally injected with a mixture of (b,d) 6.0 × 10⁸ vp AAV-S and 1.8 × 10¹⁰ vp AAV-R whereas the left eyes were injected with (a,c) 6.0 × 10⁸ vp AAV-C. Note that AAV-S and AAV-C coexpress enhanced green fluorescent protein (EGFP). Eyes were fixed, whole mounted, and transduced areas identified by EGFP fluorescence and excised. The excised retinal samples were postfixed and processed for transmission electron microscopy (TEM). Semi- and ultrathin sections were analyzed by (a,b) light microscopy or (c,d) TEM. Combined suppression and replacement therapy resulted in preservation of rod photoreceptor outer segments (OS), which extended to the retinal pigment epithelium (RPE; b and d). In contrast, in the control retina, only membranous debris (*) was detected between the RPE and the inner nuclear layer (INL) whereas the outer nuclear layer (ONL) was not present (a,c). IS, inner segment layer, GCL, ganglion cell layer. Bars = 25 µm (a,b) and 2 µm (c,d).