Deletion of RetGC isozymes slows degeneration of Rd3−/−photoreceptors.A, representative post-mortem retinal morphology in Rd3−/− (left) and Rd3−/−RetGC1−/− (right) littermates at 2.5 months of age. Photoreceptor outer nuclei layer (ONL) thickness hereafter is marked by the yellow arrow; other histological layers hereafter are as follows: GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; IS, inner segments; OPL, outer plexiform layer; OS, rod outer segments; RPE, retinal pigment epithelium. B, representative in vivo OCT of the retina at 1, 2, and 4 months of age in (top to bottom) wildtype, Rd3−/−, Rd3−/−RetGC1−/−, and Rd3−/−RetGC2−/− mice; note the markedly improved Rd3−/− ONL thickness after deletion of either RetGC isozyme at 2 and 4 months; the location of photoreceptors is schematically shown in blue; bars in either direction—100 μm. C, progressing reduction of ONL thickness measured in vivo using OCT: wildtype (•), Rd3−/− (◯), RetGC1−/− (✕), RetGC2−/− (□), Rd3−/−RetGC1−/− (◆), and Rd3−/−RetGC2−/−(△); each data point is an average of ten measurements of ONL in retinal OCT sections per different mouse of indicated genotype; data fitted assuming exponential decay; note the much slower progression of the ONL loss in Rd3−/− after deletion of RetGC1 or RetGC2. OCT, optical coherence tomography; RetGC, the retinal membrane guanylyl cyclase.