Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis

Retinal neovascularization is a leading cause of blindness.While current anti-VEGF drugs effectively inhibit pathological angiogenesis,some patients develop resistance or reduced responsiveness to treatments over time,leading to diminished effectiveness.In this study,we identified high activation of the cGAS-STING signaling pathway,which exacerbated pathological neovascularization and vessel leakage.We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug.The hydrogel,made of Pluronic F127 demonstrated excellent transparency and biocompatibility.Importantly,the thermo-sensitive property allowed for precise spatial release of the drug,extending the effective treatment duration of C-176,which suppressed STING activation in the retina,reduced inflammation and protected retinal tissue.Hydro^(C-176) effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors,highlighting its enhanced efficacy.While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy,Hydro^(C-176) exhibited more robust capabilities in regulating ocular microenvironmental inflammation.This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation,potentially improving patients’response to traditional treatment.These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.