Figure 4.

Cone degeneration occurs before measurable loss of retinal thickness

(A) Expression of PNA (a cone-specific marker, green) in wild-type and untreated Nmnat1^V9M/V9M mice at 2, 3, and 4 weeks of age. Bottom panels are counterstained with DAPI (blue). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer; RPE, retinal pigment epithelium. Scale bar indicates 20 μm. (B) Quantification of the number of cones per area based on PNA staining. Statistically significant differences are noted by red asterisks (n $=$ 3 WT and n $=$ 3 Nmnat1^V9M/V9M mice for each age, two-way ANOVA, multiple comparisons, p < 0.05, error bars represent the SEM, points represent the number of cones per image from a single mouse). (C) Expression of PNA (red) in wild-type (left panel) and Nmnat1^V9M/V9M retinas (middle panel) co-injected with scAAV9.CASI.hNMNAT1.WPRE and AAV2/9.CMV.EGFP or untreated (right panel) at 9 months of age. Green labeling indicates expression of EGFP from AAV2/9.CMV.EGFP. Bottom panels are counterstained with DAPI (blue). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer; RPE, retinal pigment epithelium. Scale bar indicates 20 μm.