Tyrosol protects RPE cells from HO-induced oxidative damage in vitro and in vivo through activation of the Nrf2/HO-1 pathway.

Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is a critical factor in the pathogenesis of age-related macular degeneration (AMD). Tyrosol is a phenolic compound with antioxidant properties, but its protective effect against oxidative stress-induced AMD and its underlying mechanisms are unknown. The aim of this study was to investigate the protective effects of tyrosol on hydrogen peroxide (HO)-induced retinal damage and demonstrate its underlying mechanisms in ARPE-19 cells and C57BL/6J mice retinas. We found that tyrosol significantly enhanced the survival of ARPE-19 cells under HO-induced oxidative stress in a concentration-dependent manner. It effectively attenuated the production of reactive oxygen species (ROS) and lipid peroxides, while also counteracting the associated reduction in glutathione (GSH) concentration and superoxide dismutase (SOD) activity. Furthermore, pretreatment with tyrosol ameliorated apoptosis-related damage in ARPE-19 cells induced by HO and normalized the levels of apoptosis-related proteins. Notably, tyrosol significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzymes heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone 1 (NQO1). Interestingly, in vivo study demonstrated that tyrosol administration effectively improved retinal function and morphology in HO-exposed mice, restored the thickness of the outer nuclear layer and inner core layer, and normalized the expression of proteins Bax, cleaved caspase-3, and Nrf2, which was consistent with the results of in vitro experiments. Overall, our findings suggest that tyrosol can protect RPE cells from oxidative stress damage by activating the Nrf2/HO-1 pathway, which may be a promising new strategy for the treatment of AMD.