Following OCT examination at 10 weeks after treatment,
rd11 mice were sacrificed and eyes enucleated for histology. Hematoxylin and eosin staining of AAV8 (Y733F)-smCBA-
Lpcat1–treated and contralateral, untreated controls
rd11 retinas confirmed OCT results. Using a retina from a representative
rd11 mouse that received >90% retinal detachment after injection; that is, had a large area of retina exposed to the vector, light microscopy at low-magnification revealed a relatively normal outer nuclear layer (ONL) throughout the retina (
Fig. 4A, left). In contrast, it was difficult to visualize any ONL in the untreated eye of the same
rd11 mouse (
Fig. 4B, right). Higher-magnification images showed that approximately 2/3 of the normal outer segment length and ONL thickness were maintained in the treated
rd11 retinas compared to a normal uninjected C57BL/6J retinas (
Fig. 4B, left and middle). Meanwhile, there was only one incomplete layer of nuclei in the ONL of the untreated eye from the same
rd11 mouse (
Fig. 4B, right). In addition, the outer plexiform layer also became thinner in the untreated
rd11 retina (
Fig. 4B, right) relative to that seen in the partner-treated eye (
Fig. 4B, middle). Significant differences were found in retinal thickness among the untreated, treated
rd11, and uninjected normal C57BL/6J mice: 0.099 ± 0.007, 0.151 ± 0.016, and 0.213 ± 0.017 mm, respectively, 1-way ANOVA,
F = 48.652,
df = 2,
P < 0.001. The LSD analysis revealed a statistical difference between the untreated and treated
rd11 retina (
P = 0.004), and a similar significant difference also was found between treated
rd11 and normal uninjected C57BL/6J retina (
P = 0.002).