期刊
REDOX BIOLOGY
卷 62, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2023.102687
关键词
Glaucoma; Retinal ganglion cell; Mitochondrial dynamics; Dynamin-related protein 1; PANoptosis
Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell loss and visual field defects. High intraocular pressure (ph-IOP) is an important risk factor for glaucoma and triggers specific molecular pathways leading to retinal ganglion cell death. This study investigates the role of the ERK1/2-Drp1-reactive oxygen species (ROS) axis in retinal ganglion cell death and the relationship between Drp1-mediated mitochondrial dynamics and PANoptosis in ph-IOP injury. The findings suggest that inhibiting the ERK1/2-Drp1-ROS pathway may be a potential therapeutic strategy for ph-IOP-induced injuries.
Glaucoma is a common neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) loss and visual field defects. Pathologically high intraocular pressure (ph-IOP) is an important risk factor for glau-coma, and it triggers molecularly distinct cascades that control RGC death and axonal degeneration. Dynamin-related protein 1 (Drp1)-mediated abnormalities in mitochondrial dynamics are involved in glaucoma patho-genesis; however, little is known about the precise pathways that regulate RGC injury and death. Here, we aimed to investigate the role of the ERK1/2-Drp1-reactive oxygen species (ROS) axis in RGC death and the relationship between Drp1-mediated mitochondrial dynamics and PANoptosis in ph-IOP injury. Our results suggest that inhibiting the ERK1/2-Drp1-ROS pathway is a potential therapeutic strategy for treating ph-IOP-induced injuries. Furthermore, inhibiting Drp1 can regulate RGC PANoptosis by modulating caspase3-dependent, nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3(NLRP3)-dependent, and receptor-interacting protein (RIP)-dependent pathways in the ph-IOP model. Overall, our findings provide new insights into possible protective interventions that could regulate mitochondrial dynamics to improve RGC survival.
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