These authors contributed equally to this work.
Annatto prevents retinal degeneration induced by endoplasmic reticulum stress in vitro and in vivo
Version of Record online: 30 MAY 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 5, pages 713–724, May 2012
How to Cite
Tsuruma, K., Shimazaki, H., Nakashima, K.-i., Yamauchi, M., Sugitani, S., Shimazawa, M., Iinuma, M. and Hara, H. (2012), Annatto prevents retinal degeneration induced by endoplasmic reticulum stress in vitro and in vivo. Mol. Nutr. Food Res., 56: 713–724. doi: 10.1002/mnfr.201100607
- Issue online: 30 MAY 2012
- Version of Record online: 30 MAY 2012
- Manuscript Accepted: 13 JAN 2012
- Manuscript Revised: 4 JAN 2012
- Manuscript Received: 6 SEP 2011
- ER stress;
Annatto (Bixa orellana) seeds have been used as a colorant in butter and in a variety of other foods. In this study, we investigated the amelioration of retinal damage by an acetone extract of annatto (A-ext.), bixin (a main component of annatto), and four bixin derivatives (Bx-1, Bx-2, Bx-3, and Bx-4) that we have synthesized.
Methods and results
We used cultured retinal ganglion cells (RGC-5) to examine in vitro effects of A-ext. on stress pathways, focusing on intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, caspase-3 activation, and cell membrane damage. In vivo retinal damage in mice following intravitreous injection of tunicamycin was evaluated by counting the cell numbers in the ganglion cell layer (GCL) and measuring the thickness of outer nuclear layer (ONL). A-ext., bixin, and Bx-1 treatment inhibited both tunicamycin- and H2O2-induced cell death. Bixin derivatives also inhibited tunicamycin-induced cell death. Treatment with A-ext., bixin, and Bx-1 reduced tunicamycin-induced caspase-3 activity and inhibited the inversion of phosphatidylserine, an early apoptotic event without antioxidant effect or reduction of ER stress itself. A-ext., bixin, and Bx-1 significantly inhibited the tunicamycin-induced loss of cells from the GCL, and these materials also suppressed the tunicamycin-induced thinning of ONL.
A-ext., its main component bixin, and bixin derivatives may therefore be useful for preventive and therapeutic treatment of retinal-related diseases.