Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation.

ABSTRACT: Oxidative stress and hypoxia lead to dysfunction of retinal pigment epithelium (RPE) cells and are hallmarks of diseases such as age-related macular degeneration (AMD), the most common blinding disease in the elderly population. We have previously shown that a combination of these two risk factors, i.e. hypoxidative stress, exacerbates RPE cell death by ferroptosis. Hypoxia leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. In the present study, we have therefore investigated the roles of HIF-1 and HIF-2 in RPE cell death in a human RPE cell line under hypoxidative stress. For this purpose, we conducted siRNA-mediated knockdowns of the α-subunits of HIF-1 and HIF-2. We found that especially iron metabolism, in particular

SUBMITTER: Schubert A 

PROVIDER: S-EPMC12354819 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature