RGC-specific NMNAT2 overexpression significantly promotes neuronal NAD+ production and survival of both RGC somata and axons in the SOHU glaucoma model
(A) Relative NAD+ levels of retinas and ONs from naive, SOHU glaucoma at 1 week after SO injection (1 wpi), and SOHU glaucoma mice with NMNAT1 or NMNAT2 overexpression, acquired by LC/MS analysis. n = 5 in all the groups. Data are presented as means ± SD; ∗p < 0.05, ∗∗p < 0.01, one-way ANOVA with Dunnett's multiple comparisons test. (B) Representative OCT images of SOHU glaucoma mouse retinas at 3 wpi. Ganglion cell complex (GCC) includes RNFL, GCL, and IPL indicated as double-end arrows. (C) Quantification of GCC thickness measured by OCT at 3 wpi, represented as percentage of GCC thickness in the SOHU eyes compared with the sham contralateral control eyes. n = 20 in both groups. Data are presented as means ± SD; ∗∗∗p < 0.001, two-tailed unpaired t test. (D) Upper panel: representative confocal images of peripheral flat-mounted retinas showing surviving RBPMS-positive (red) RGCs at 3 wpi. Scale bars, 20 μm. Lower panel: light microscopic images of semi-thin transverse sections of ON with PPD staining at 3 wpi. Scale bars, 10 μm. (E) Quantification of surviving RGCs somata and axons at 3 wpi, represented as percentage of glaucomatous eyes compared with the sham contralateral control eyes. n = 19 in both groups. Data are presented as means ± SD; ∗∗∗∗p < 0.0001, two-tailed unpaired t test. See also Figure S3.