Purple rice extract and its constituents suppress endoplasmic reticulum stress-induced retinal damage in vitro and in vivo.

OBJECTIVE

Endoplasmic reticulum (ER) stress has been implicated as a cause of various neurodegenerative diseases. We evaluated the protective effects of purple rice (Oryza sativa L.) bran extract (PRE) and its constituents, namely cyanidin, peonidin, and a newly isolated compound 2-hydroxy-5-[(3S)-3-hydroxybutyl]phenyl-β-D-glucoside (HHPG), against tunicamycin-induced retinal damage.

METHODS

In an in vitro experiment, protective effects of PRE, cyanidin and HHPG on cultured retinal ganglion cells (RGC-5), which were damaged by treatment with H(2)O(2) or tunicamycin for 24 h, were evaluated. We also investigated the underlying mechanism by examining expressions of ER stress-related proteins, such as immunoglobulin heavy-chain binding protein (BiP) and C/EBP homologous protein (CHOP), and activation of caspase-3 induced by tunicamycin. In an in vivo experiment, mice retinal damage was induced by intravitreous injection of tunicamycin as revealed by histological analysis using hematoxylin-eosin staining.

RESULTS

The viability of H(2)O(2) or tunicamycin-treated RGC-5, assessed using the tetrazolium salt (WST-8) assay, was improved by treatment with PRE, cyanidin, and HHPG, respectively. PRE did not affect tunicamycin-induced expressions of BiP or CHOP. However, PRE, cyanidin, and HHPG suppressed tunicamycin-induced caspase-3 activation. Histological analysis using hematoxylin-eosin staining showed that intravitreous injection of PRE significantly suppressed the tunicamycin-induced degeneration of retinal ganglion cells in mice.

CONCLUSIONS

These findings indicate that PRE, cyanidin, and HHPG suppress tunicamycin-induced retinal ganglion cell death at least partly by inhibiting activation of caspase-3, suggesting that PRE and its main constituents prevent retinal disease caused by ER stress.