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KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy by inhibiting phosphorylation-driven PRDX1 phase separation - PubMed

4 hours ago
  • #ferroptosis
  • #retinal endothelial cells
  • #familial exudative vitreoretinopathy
  • KIF11 prevents retinal endothelial ferroptosis in familial exudative vitreoretinopathy (FEVR).
  • FEVR is a hereditary disorder causing severe vision loss in infants and young children, with 40% of cases linked to Norrin/β-catenin pathway mutations.
  • KIF11 is identified as a key downstream effector in retinal endothelial cells via RNA sequencing analyses.
  • β-catenin/KIF11 deficiency induces autophagy-accompanied ferroptosis, contributing to FEVR pathogenesis.
  • KIF11 binds PRDX1, and its disruption leads to Src-mediated PRDX1 phosphorylation and liquid-liquid phase separation.
  • Ferroptosis inhibitor ferrostatin-1 and non-phosphorylatable PRDX1 overexpression partially rescue vascular defects in FEVR-associated mice.
  • The study highlights the β-catenin/KIF11/PRDX1 axis and suggests ferroptosis-targeting and antioxidant strategies as potential therapies.