Irigenin Modulates BL-Induced Pyroptosis in Retinal Pigment Epithelial Cells Through p38 MAPK and NFκB Pathways

Area of Science:

• Ophthalmology and Vision Science
• Cell Biology
• Pharmacology

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, linked to inflammation.
• Blue light (BL) exposure induces damage in retinal pigment epithelial cells, contributing to AMD pathogenesis.
• A2E-laden ARPE-19 cells are a model for studying AMD-related cellular damage.

Purpose of the Study:

• To investigate the protective effects of irigenin against blue light-induced damage in A2E-laden ARPE-19 cells.
• To elucidate the anti-inflammatory and anti-pyroptotic mechanisms of irigenin in retinal cells.
• To assess the therapeutic potential of irigenin for preventing AMD.

Main Methods:

• ARPE-19 cells were pretreated with varying concentrations of irigenin before exposure to blue light.
• Cytotoxicity and epithelial barrier function were assessed.
• Expression of inflammatory cytokines, NLRP3 inflammasome components (NLRP3, ASC, GSDMD), and caspase-1 activity were measured.
• NFκB and p38 MAPK signaling pathways were analyzed via phosphorylation and translocation studies.

Main Results:

• Irigenin pretreatment significantly reduced blue light-induced cytotoxicity and preserved epithelial barrier function in a dose-dependent manner.
• Irigenin inhibited the expression of pro-inflammatory cytokines and suppressed NLRP3 inflammasome activation (reduced NLRP3, ASC, GSDMD, and caspase-1 activity).
• Irigenin effectively inhibited the NFκB signaling pathway and reduced p38 MAPK phosphorylation.

Conclusions:

• Irigenin demonstrates significant protective effects against blue light-induced damage in retinal pigment epithelial cells.
• Irigenin ameliorates cellular damage by modulating inflammatory responses and pyroptosis via the NLRP3 and NFκB pathways.
• These findings highlight irigenin as a potential therapeutic agent for AMD prevention.