Fig. 4

Axonal spheroids/end bulbs in retina, papilla, and optic nerve. Sections through the optic nerve head (a, b), ganglionic cell layer (c-e, consecutive sections) and retinal nerve fiber layer (f) were reacted with antibodies against APP (a-c, f), iNOS (d), and AQP4 (e). Antibody binding is shown in brown, and the nuclei are revealed by counterstaining with hematoxylin. The tissue sections derived from Lewis rats injected with AQP4_268–285-specific T cells and either NMO-IgG (a,c-f) or co-IgG (b). APP⁺ axonal spheroids/endbulbs can be seen upon the induction of inflammation by AQP4_268–285-specific T cells in presence and absence of NMO-IgG (a-c, f), and coincide with iNOS⁺ macrophages (d) and essentially normal AQP4 expression (e). Bars = 25 μm. g Numbers of APP⁺ spheroids/endbulbs in the most affected lesion per rat, found in retina (RET), papilla (PAP), and central or peripheral parts of optic nerve cross sections (cON or pON, respectively), as determined from 11 rats injected with T cells and NMO-IgGs, and from 8 rats injected with NMO-IgGs only. The numbers of APP⁺ spheroids/end bulbs were significantly higher in retina and papilla compared to central and peripheral optic nerve (p = 0,002, Mann-Whitney U-test). h Numbers of APP⁺ spheroids/endbulbs in the most affected retinal and papillary lesion per rat, found in animals injected with AQP4_268–285-specific T cells/NMO-IgG (n = 15; NMO-IgG from 3 different sources), AQP4_268–285-specific T cells/control IgG (coIgG) (n = 8) and NMO-IgG only (n = 12). The differences between the T cell injected groups and the group receiving NMO-IgG only were significant (**p = 0.006 and *p = 0.025, respectively; Mann-Whitney U-test with Bonferroni-Holm correction)