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Abstract #117122 Published in IGR 24-4
SOX9 depletion attenuates retinal ganglion cell ferroptosis through blocking ERK/p38 signaling
Wei W; Zhang Y; Li L; Yang JTissue & cell 2024; 87: 102315
BACKGROUND: Retinal ischemia-refusion (I/R) is a leading cause of irreversible blindness worldwide. This study aims to explore the regulatory role of SOX9 in retinal I/R injury, and attempts to elucidate its potential regulatory mechanism. METHODS: Retinal I/R injury model was established in vivo, and the histological changes was examined by hematoxylin and eosin (H&E) staining and immunofluorescent assay was performed to examine SOX9 expression. Oxygenation-glucose deprivation/reoxygenation (OGD/R)-induced retinal ischemia/reperfusion (I/R) injury in 661 W cells was constructed as an in vitro cellular model of glaucoma. The production of cytokines, lactate dehydrogenase (LDH) and the antioxidant enzymes were assessed by their commercial kits. Cellular reactive oxygen species (ROS) and lipid ROS was detected using DCFH-DA and C11-BODIPY 581/591 staining, respectively. Lipid peroxidation and Fe level were detected to assess the ferroptosis level. Protein expression was examined by western blot. LM22B-10, the agonist of ERK signaling, was used to pretreat 661 W cells for mechanism investigation. RESULTS: SOX9 was aberrantly upregulated following retinal I/R injury both in vivo and in vitro. SOX9 knockdown exerted a protective role against OGD/R-triggered oxidative stress, inflammatory response and ferroptosis in 661 W cells. Further, ERK/p38 signaling was activated in 661 W cells following OGD/R induction, which was repressed by SOX9 knockdown, and the ERK signaling agonist partially counteracted the protective role of SOX9 knockdown against oxidative stress, inflammatory response and ferroptosis in OGD/R-induced 661 W cells. CONCLUSION: Collectively, inhibiting SOX9 to block oxidative stress, inflammation and ferroptosis by inactivating ERK/p38 signaling might be effective to prevent retinal I/R injury, thereby alleviating glaucoma.
Ophthalmology Department, Inner Mongolia Autonomous Region People's Hospital, Hohhot 010017, Inner Mongolia Autonomous Region, China.
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