Chen Xi, Rong Yan, Jiang Yuxian, Zhang Qiuxiang, Xiang Sifei, Chen Zhiqi, Chen Wei, Zhang Hong, Deng Chaohua, Wang Junming
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ophthalmic Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):46. doi: 10.1167/iovs.66.4.46.
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.
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.
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.
In conclusion, this study demonstrates that vitamin K1 exerts a protective effect by modulating microglial ferroptosis, thereby alleviating acute ocular hypertension-induced retinal inflammation.
青光眼是全球不可逆性失明的主要原因，是一组以视神经萎缩和视野缺损为特征的疾病。急性眼压升高是视网膜炎症和视神经损伤的关键驱动因素，常伴有小胶质细胞活化和铁死亡途径失调。维生素K1是一种脂溶性维生素，具有抗炎和抗氧化特性，并有调节铁死亡的潜力。然而，其在急性眼压升高后减轻视网膜炎症的机制仍不清楚。
在体内，我们建立了急性高眼压小鼠模型，以评估维生素K1对视网膜和视觉功能的保护作用。采用转录组测序来探索维生素K1发挥作用的潜在机制。免疫荧光和蛋白质印迹法用于评估视网膜炎症并观察小胶质细胞中的铁死亡。在体外，我们建立了BV2细胞氧糖剥夺再灌注（OGDR）模型，以研究维生素K1对小胶质细胞铁代谢和炎症的调节作用。
我们的研究结果表明，急性眼压升高导致小胶质细胞活化，同时伴有小胶质细胞铁过载和铁死亡。进一步分析显示，小胶质细胞铁死亡伴随着炎性细胞因子基因表达和蛋白水平的上调。然而，维生素K1干预可抑制小胶质细胞铁死亡，减轻视网膜炎症，减少视网膜神经节细胞（RGC）丢失，并保护视觉功能。
总之，本研究表明维生素K1通过调节小胶质细胞铁死亡发挥保护作用，从而减轻急性高眼压诱导的视网膜炎症。
