视神经损伤
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Figure 1｜Immunofluorescence analysis of surviving RGCs and macrophages in the retina after IOP elevation and treatment with CK2 inhibitors.
Viable RGCs in rats with acute IOP elevation were labeled by FG (Figure 1A and B). The average number of surviving RGCs was significantly reduced in rats with IOP elevation by 2.64-fold (P < 0.001), compared with that in the control rats. However, the average number of surviving RGCs was significantly rescued by intravitreal injection of either CK2 inhibitor, TBB or DMAT, by 2.61- and 2.55-fold (P < 0.001), respectively, compared with that in rats with IOP elevation (Figure 1A and B). These results suggested that CK2 inhibition enhanced RGCs survival after acute IOP elevation. Because mild inflammation resulting from macrophage infiltration and activation has been shown to promote RGCs survival (Leon et al., 2000; Williams et al., 2017; Bari? and Tezel, 2019; Baudouin et al., 2021), we evaluated macrophage infiltration after IOP elevation and CK2 inhibition by immunofluorescence analysis. The number of macrophages was significantly increased after IOP elevation by 15.11-fold (P < 0.001), compared with that in the control rats, while the number of macrophages was significantly reduced byth intravitreal injections of TBB or DMAT by 9.72- and 11.18-fold (P < 0.001), respectively, compared with that in the vehicle control group (without TBB or DMAT; Figure 1A and C). These results suggest that the CK2 inhibition-mediated promotion of RGCs survival after acute IOP elevation could be associated with inhibition of macrophage activation.
To further validate the direct effect of macrophage activation on acute IOP elevation, zymosan, a macrophage activator, was intravitreally injected into rat eyes after acute IOP elevation. The number of macrophages markedly increased with the application of zymosan by 4.87-fold (P < 0.001), compared with that in rats that underwent acute IOP elevation but were not treated with zymosan (Figure 1A and C). Also, the number of macrophages in rats with acute IOP elevation and treated with TBB or DMAT and zymosan were significantly decreased by 2.12-fold (P < 0.001) or 1.75-fold (P < 0.05) compared with that in rats with acute IOP elevation treated with zymosan (Figure 1A and C). RGCs survival was significantly reduced in rats that received zymosan treatment by 4.76-fold (P < 0.05), compared with that in rats that underwent acute IOP elevation but were not treated with zymosan (Figure 1A and B). The number of RGCs was significantly increased in rats with acute IOP elevation and treated with TBB or DMAT and zymosan by 2.56-fold (P < 0.05) or 2.46-fold (P > 0.05) compared with that in rats with acute IOP elevation treated with zymosan (Figure 1A and B). Collectively, these results indicate that macrophage activation reduced RGCs survival after acute IOP elevation.