Purpose: Glaucoma is the leading cause of irreversible blindness worldwide and encompasses a group of diseases characterized by optic nerve atrophy and visual field defects. Acute intraocular pressure (IOP) elevation is a key driver of retinal inflammation and optic nerve damage, often accompanied by microglial activation and dysregulated ferroptosis pathways. Vitamin K1, a fat-soluble vitamin, possesses anti-inflammatory and antioxidant properties, and has the potential to regulate ferroptosis. However, its mechanisms in alleviating retinal inflammation following acute IOP elevation remain unclear.
Methods: In vivo, we established a mouse model of acute ocular hypertension to evaluate the protective effects of vitamin K1 on the retina and visual function. Transcriptome sequencing was used to explore the underlying mechanisms by which vitamin K1 exerts its effects. Immunofluorescence and Western blot were used to assess retinal inflammation and observe ferroptosis in microglia. In vitro, we developed a BV2 cell OGDR model to investigate the regulatory effects of vitamin K1 on iron metabolism and inflammation in microglia.
Results: Our findings demonstrated that acute IOP elevation led to microglial activation, along with iron overload and ferroptosis in microglia. Further analyses revealed that microglial ferroptosis was accompanied by an upregulation of inflammatory cytokine gene expression and protein levels. Vitamin K1 intervention, however, inhibited microglial ferroptosis, alleviated retinal inflammation, minimized retinal ganglion cell (RGC) loss, and protected visual function.
Conclusions: In conclusion, this study demonstrates that vitamin K1 exerts a protective effect by modulating microglial ferroptosis, thereby alleviating acute ocular hypertension-induced retinal inflammation.