Bilberry and its main constituents have neuroprotective effects against retinal neuronal damage in vitro and in vivo

Mol Nutr Food Res. 2009 Jul;53(7):869-77. doi: 10.1002/mnfr.200800394.


Our aim was to determine whether a Vaccinium myrtillus (bilberry) anthocyanoside (VMA) and/or its main anthocyanidin constituents (cyanidin, delphinidin, and malvidin) can protect retinal ganglion cells (RGCs) against retinal damage in vitro and in vivo. In RGC cultures (RGC-5, a rat ganglion cell-line transformed using E1A virus) in vitro, cell damage and radical activation were induced by 3-(4-morpholinyl) sydnonimine hydrochloride (SIN-1, a peroxynitrite donor). Cell viability was measured using a water-soluble tetrazolium salt assay. Intracellular radical activation within RGC-5 cells was evaluated using 5-(and-6)-chloromethyl-2,7-dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA). Lipid peroxidation was assessed using the supernatant fraction of mouse forebrain homogenates. In mice in vivo, we evaluated the effects of VMA on N-methyl-D-aspartic acid (NMDA)-induced retinal damage using hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stainings. VMA and all three anthocyanidins (i) significantly inhibited SIN-1-induced neurotoxicity and radical activation in RGC-5, (ii) concentration-dependently inhibited lipid peroxidation in mouse forebrain homogenates. Intravitreously injected VMA significantly inhibited the NMDA-induced morphological retinal damage and increase in TUNEL-positive cells in the ganglion cell layer. Thus, VMA and its anthocyanidins have neuroprotective effects (exerted at least in part via an anti-oxidation mechanism) in these in vitro and in vivo models of retinal diseases.

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Apoptosis / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Molsidomine / analogs & derivatives
  • Molsidomine / toxicity
  • N-Methylaspartate / toxicity
  • Neuroprotective Agents / pharmacology*
  • Prosencephalon / drug effects
  • Prosencephalon / metabolism
  • Retinal Ganglion Cells / drug effects*
  • Vaccinium myrtillus* / chemistry


  • Anthocyanins
  • Neuroprotective Agents
  • linsidomine
  • N-Methylaspartate
  • Molsidomine