Hydrogen sulfide protects retinal pigment epithelium cells against ferroptosis through the AMPK- and p62-dependent non-canonical NRF2-KEAP1 pathway.

Oxidative stress-induced ferroptosis of retinal pigment epithelium (RPE) cells contributes to retinal degenerative diseases. The antioxidant molecule hydrogen sulfide (HS) regulates oxidative stress response, but its effect on the ferroptosis of RPE cells is unclear. In this study, sodium hydrosulfide (NaHS) was used as an exogenous HS donor to intervene tert-butyl hydroperoxide (t-BHP)-induced ferroptosis of APRE-19 cells.

Pharmacological inhibition of sphingolipid synthesis reduces ferroptosis by stimulating the HIF-1 pathway.

Ferroptosis is crucial to the pathology of many neurological diseases. Here, we found pre-treatment with myriocin, an inhibitor of synthesis of sphingolipid, significantly decreased the erastin- or glutamate-induced ferroptosis of HT22 cells without requiring the recovery of intracellular glutathione. The transcriptome analysis of HT22 cells treated with or without myriocin identified the hypoxia-inducible factor 1 (HIF-1) pathway as a prime and novel drug target.

Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells.

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway.