GPR40 Attenuates Age-Related Macular Degeneration by Suppressing Retinal Microglial NLRP3 Inflammasome Activation Via ERK Signaling.

ABSTRACT: Retinal neuroinflammation is a key pathological feature of age-related macular degeneration (AMD), primarily driven by aberrant microglial cell activation. The expression and role of G-protein-coupled receptor 40 (GPR40), in AMD remain unclear. To investigate this pathology, we established a sodium iodate-induced mouse model of non-exudative AMD and performed in vitro experiments using LPS-stimulated microglial cells. The results showed that activation of the GPR40 receptor significantly promoted the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, effectively inhibiting neuroinflammation. Mechanistic studies revealed that GPR40 negatively regulates the ERK signaling pathway, inhibiting NLRP3 inflammasome activation and the rele

SUBMITTER: Tan X 

PROVIDER: S-EPMC12832595 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature