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

Doc Ophthalmol. 2019 Apr;138(2):125-135. doi: 10.1007/s10633-019-09676-9. Epub 2019 Feb 11.

Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusion: In conclusion, fisetin is able to promote the visual functions of DBA/2J mice by inhibiting NF-κB activation.

Keywords: DBA/2J mouse; Fisetin; Glaucoma; Nuclear factor kappa-B (NF-κB); Retinal ganglion cells (RGCs).

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Blotting, Western
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Electroretinography
  • Enzyme-Linked Immunosorbent Assay
  • Evoked Potentials, Visual / physiology*
  • Female
  • Flavonoids / therapeutic use*
  • Flavonols
  • Glaucoma / metabolism
  • Glaucoma / physiopathology
  • Glaucoma / prevention & control*
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Intraocular Pressure / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • NF-kappa B / metabolism
  • Retina / physiopathology*
  • Retinal Ganglion Cells
  • Tonometry, Ocular

Substances

  • Antioxidants
  • Cytokines
  • Flavonoids
  • Flavonols
  • NF-kappa B
  • fisetin