STING activation induces polarized cytokine secretion of IFN-β and IL-17A promoting photoreceptor death and choroidal disruption in age-related macular degeneration - PubMed
5 hours ago
- #Age-related macular degeneration
- #Cytokine secretion
- #STING pathway
- STING activation plays a dual role in age-related macular degeneration (AMD), providing cytoprotection in healthy tissue but driving pathogenic inflammation during early AMD progression.
- Immunohistochemical analysis of human eyes shows stage-dependent cytoplasmic STING upregulation with parallel IFN-β activation.
- Patient-derived iPSC-RPE cells exhibit polarized cytokine secretion: apical IFN-β triggers photoreceptor apoptosis, while basal IL-17A compromises choroidal neovascularization.
- The Cryba1 conditional knockout mouse model confirms STING-driven IL-17A expression, and Il17a knock-in mice show vascular alterations.
- STING activation creates a pathogenic feed-forward loop between interferons and IL-17A, contributing to AMD progression.
- Single-cell transcriptomics reveals metabolic and phototransduction dysregulation following AAV2-mediated IFN-β overexpression.
- Pharmacological STING inhibition with SN-011 and genetic approaches demonstrate therapeutic rescue in AMD models.
- Cryba1/Sting double heterozygous mice maintain homeostatic gene expression, preserving retinal architecture and function.
- STING is identified as a master regulator controlling multiple AMD pathologies through spatially organized inflammation.