Vitamin K1 Alleviates Retinal Inflammation Following Acute Ocular Hypertension by Modulating Microglial Ferroptosis

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Glaucoma is a leading cause of irreversible blindness globally.
• Elevated intraocular pressure (IOP) triggers retinal inflammation and optic nerve damage via microglial activation and ferroptosis.
• Vitamin K1 has anti-inflammatory and antioxidant properties, but its role in ocular hypertension is unclear.

Purpose of the Study:

• To investigate the protective effects of Vitamin K1 on retinal inflammation and visual function following acute IOP elevation.
• To elucidate the underlying mechanisms of Vitamin K1's action, focusing on microglial ferroptosis.

Main Methods:

• Established a mouse model of acute ocular hypertension.
• Utilized transcriptome sequencing to identify molecular pathways.
• Employed immunofluorescence and Western blot to analyze retinal inflammation and microglial ferroptosis.
• Used an in vitro BV2 cell model to study Vitamin K1's effect on iron metabolism and inflammation.

Main Results:

• Acute IOP elevation induced microglial activation, iron overload, and ferroptosis.
• Microglial ferroptosis correlated with increased inflammatory gene and protein expression.
• Vitamin K1 treatment inhibited microglial ferroptosis, reduced retinal inflammation, and protected retinal ganglion cells (RGCs) and visual function.

Conclusions:

• Vitamin K1 demonstrates a protective effect against acute ocular hypertension-induced retinal damage.
• This protection is mediated by the modulation of microglial ferroptosis, leading to reduced inflammation.