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

AimsEndoplasmic 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.Main methodsIn an in vitro experiment, protective effects of PRE, cyanidin and HHPG on cultured retinal ganglion cells (RGC-5), which were damaged by treatment with H2O2 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.Key findingsThe viability of H2O2 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.SignificanceThese 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.