Fig. 9

The regenerative thickening of the innermost retinal composite layer upon therapeutic treatment is driven by restoration of dendritic arborization within the IPL. a Histological quantification of thickness of the IPL (left) and NFL/GCL (right) in Wt, PLPmut, and PLPmut mice after therapeutic treatment identifies the IPL as the responsible layer for the “regenerative” thickening. b Left, flat mount preparations of retinae. SMI32+ retinal ganglion cells display robust dendritic arborization in Wt mice (white icon) while the same cell types of untreated PLPmut mice (dark-gray icon) show “fragile” arbors of reduced extension and abundant degenerative varicosities (arrowheads). Therapeutic treatment (yellow icon) partially restored dendritic arborization and reduced numbers of degenerative varicosities. Middle, top: SMI32 immunofluorescence on a transverse section of the retina of a Wt mouse. A subpopulation of retinal ganglion cells in the GCL, their fasciculating axons in the NFL and their dendritic trees protruding into the IPL are visible. Middle, below: SMI32 immunofluorescence on transverse sections of the IPLs of Wt, PLPmut, and therapeutically treated PLPmut mice. Note “re-appearance” of SMI32-immunoreactivity reflecting regenerative dendritic trees in the IPL of the treated PLPmut mice. Right, quantification of SMI32+ dendritic areas in Wt, PLPmut, and therapeutically treated PLPmut mice. c Synaptophysin immunoreactivity in the IPLs of Wt, untreated and therapeutically treated PLPmut mice support the view that “regenerative” thickening of the IPL upon treatment is related to restoration of dendritic trees (as shown in a, b) and of their corresponding presynaptic terminals. Scale bars, 10 μm. One-way ANOVA and Tukey’s post hoc tests. *P < 0.05, **P < 0.01, ***P < 0.001. n = 5 mice per group