7,8-Dihydroxiflavone protects retinal ganglion cells and promotes axonal regeneration through TrkB signaling pathway followed by AKT and ERK activation.

The aim of this study was to investigate the effects of 7,8-dihydroxyflavone (7,8-DHF) in protecting retinal ganglion cells (RGCs) and promoting axonal regeneration, and to explore its potential molecular mechanisms. We used three-dimensional retinal culture system and optic nerve crush (ONC) rat models in this study. The pro-axonal regenerative effect of 7,8-DHF was determined with light microscopy observation and immunofluorescence staining of Thy1.1 and GAP43. The RGC protective function of 7,8-DHF was detected by RBPMS immunofluorescent staining and TUNEL staining. The inhibition effect of 7,8-DHF on astrocyte activation was measured using GFAP immunofluorescence and Western blotting. The protein levels of p-TrkB, p-AKT and p-ERK was examined by Western blotting and immunohistochemistry. Our results revealed that 7,8-DHF significantly promoted the average density and length of regenerated neurites and suppressed the apoptosis of GCL cells in three-dimensional culture system and significantly increased the number of RBPMS-positive cells and inhibited the GFAP expression and apoptosis of GCL cells in ONC rats. Our results also revealed that 7,8-DHF activates TrkB, AKT and ERK proteins in vivo, however, these activations can be inhibited byANA-12. In conclusion, 7,8-DHF protects RGCs and promotes axonal regeneration through the TrkB signaling pathway followed by AKT and ERK activation.