Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma.

Glaucoma is a common chronic neurodegenerative disease, which could lead to visual loss. In this study, we aimed to investigate whether fisetin, a natural flavone with anti-inflammatory and antioxidant properties, is able to alleviate glaucoma.We employed a DBA/2J mouse model which was treated with or without fisetin. Pattern electroretinogram (P-ERG), visual evoked potentials (VEPs) and intraocular pressure (IOP) were evaluated. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression levels of TNF-α, IL-1β and IL-6. Western blotting was performed to assess the activation of nuclear factor kappa-B (NF-κB).We found that DBA/2J mice treated with fisetin (10-30 mg/kg) showed improved P-ERG and VEP amplitudes and reduced IOP compared to untreated DBA/2J mice. In addition, there were more survived retinal ganglion cells (RGCs) and less activated microglia in fisetin-treated DBA/2J mice than those in untreated mice. Furthermore, secreted protein levels and mRNA levels of TNF-α, IL-1β and IL-6 were significantly repressed by fisetin. The phosphorylated p65 level in the nucleus was dramatically reduced in fisetin-treated mice compared to it in untreated mice. Our results demonstrate that fisetin may exert its function through regulating cytokine productions and inhibiting NF-κB activation in the retina.In conclusion, fisetin is able to promote the visual functions of DBA/2J mice by inhibiting NF-κB activation.