Fig. 5
From: Neutral sphingomyelinase inhibition promotes local and network degeneration in vitro and in vivo
Prolonged exposure to GW4869 degrades CTB uptake and promotes visual tissue degeneration. A Example confocal micrographs from whole-mount retinas immunolabeled against BRN3A (magenta) following intravitreal injection of DMSO (left) or GW4869 for 20 days. Two days prior to endpoint, CTB (cyan) was intravitreally injected. B GW4869 significantly decreased density of BRN3A-positive RGCs (p = 0.0303) and (C) reduced CTB uptake by RGCs (p = 0.0005). N = 5 DMSO-treated retinas and 6 GW4869-treated retinas. D Example images of SC immunolabeled against NeuN following intravitreal injection of DMSO or GW4869. E GW4869 significantly reduced the density of NeuN-positive cells in the SC (p = 0.0043). N = 6 DMSO/saline treated animals and 9 GW4869/saline treated animals. (F, top) Confocal image of coronal section of superior colliculus (SC) following intravitreal injection of DMSO (left eye) or saline (right eye) and CTB. (F, bottom) Confocal images of SC following injection of GW4869 (left eye) or saline (right eye) and CTB. G Reconstructed heat map of fluorescence intensity of CTB in SC of a DMSO-treated eye (top) and a GW4869-treated eye (bottom). (H) GW4869 significantly blunted the percent of intact anterograde axonal transport of CTB to the SC (p = 0.0079). N = 5 DMSO/saline and 5 GW4869/saline animals. Statistics: (B, C, E) Mann–Whitney test, (H) t-test. Data presented as mean ± sem