Bilberry extract and anthocyanins suppress unfolded protein response induced by exposure to blue LED light of cells in photoreceptor cell line

Mol Vis. 2018 Sep 24:24:621-632. eCollection 2018.


Purpose: The purpose of this study was to investigate the effects of bilberry extract with its anthocyanins on retinal photoreceptor cell damage and on the endoplasmic reticulum (ER) stress induced by exposure to blue light-emitting diode (LED) light.

Methods: Cultured murine photoreceptor cells (661W) were exposed to blue LED light with or without bilberry extract or its anthocyanins in the culture media. Aggregated short-wavelength opsin (S-opsin) in murine photoreceptor cells was observed with immunostaining. The expression of factors involved in the unfolded protein response was examined with immunoblot analysis and quantitative real-time reverse transcription (RT)-PCR. Furthermore, cell death was observed with double staining with Hoechst 33342 and propidium iodide after dithiothreitol (DTT) treatment.

Results: Bilberry extract and anthocyanins suppressed the aggregation of S-opsin, activation of ATF4, and expression of the mRNA of the factors associated with the unfolded protein response (UPR). In addition, bilberry extract and the anthocyanins inhibited the death of photoreceptor cells induced by DTT, an ER stress inducer.

Conclusions: These findings suggest that bilberry extract containing anthocyanins can alter the effects of blue LED light and DTT-induced retinal photoreceptor cell damage. These effects were achieved by modulating the activation of ATF4 and through the suppression of the abnormal aggregation of S-opsin.

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Apoptosis
  • Blotting, Western
  • Cell Line
  • Dithiothreitol / pharmacology
  • Endoplasmic Reticulum Stress / drug effects*
  • Immunoblotting
  • Light / adverse effects*
  • Mice
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Photoreceptor Cells, Vertebrate / radiation effects*
  • Plant Extracts / pharmacology*
  • Protein Aggregation, Pathological
  • Radiation Injuries, Experimental / etiology
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / prevention & control
  • Real-Time Polymerase Chain Reaction
  • Retinal Degeneration / etiology
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / prevention & control
  • Rod Opsins / metabolism
  • Unfolded Protein Response / drug effects*
  • Vaccinium myrtillus / chemistry*


  • Anthocyanins
  • Plant Extracts
  • Rod Opsins
  • short-wavelength opsin
  • Dithiothreitol