Pathologically high intraocular pressure induces mitochondrial dysfunction through Drp1 and leads to retinal ganglion cell PANoptosis in glaucoma.
Redox Biol
; 62: 102687, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-36989574
ABSTRACT
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 glaucoma, 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 pathogenesis; 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glaucoma
/
Doenças Neurodegenerativas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Redox Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China