Work

Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis

Year: 2026

Type: article

Abstract: Purpose: To examine whether α-asarone (ASA) protects dry age-related macular degeneration (dAMD) from sodium iodate (SI) injury by modulating the P2X7-mediated NLRP3 inflammasome axis. Methods: Male Sprague-Dawley rats were treated with SI to establish a dAMD model. Retinal structure and function were evaluated using electroretinography (ERG), optical coherence tomography (OCT), and hematoxylin-eosin staining, whereas the expression of functional and inflammatory proteins was analyzed via immunofluorescence and Western blotting. Molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assays (CETSA) were performed to explore the potential interaction between ASA and P2X7. In vitro, SI-stimulated ARPE-19 cells were used to evaluate the protective effects of ASA and the involvement of P2X7 through Cell Counting Kit-8 assays, Annexin V-FITC/PI staining, Fluo-4 staining, YO-PRO-1 uptake detection, ELISA, and Western blotting. Results: ASA preserved retinal structure and function, maintained the expression of key functional proteins, suppressed microglial activation, and attenuated inflammatory responses. Computational modeling suggested a stable potential interaction between ASA and P2X7, and CETSA further supported ASA-induced modulation of P2X7 thermal stability in cells. In vitro, ASA enhanced cell viability, reduced apoptosis, attenuated Ca²⁺ influx and P2X7 macropore formation, decreased the release of inflammatory cytokines, and downregulated P2X7/NLRP3 pathway, all of which were effectively abolished by activating P2X7. Conclusions: The findings demonstrate that ASA mitigates SI-induced dAMD injury by suppressing the P2X7/NLRP3 inflammatory pathway. This study identifies a promising new therapeutic strategy for dAMD.

Source: Investigative Ophthalmology & Visual Science

DOI: 10.1167/iovs.67.12.30