Microglia-specific interleukin-4 delivery by engineered extracellular vesicles restores inner blood-retinal barrier in diabetic retinopathy via GAS6-MERTK pathway.

ABSTRACT: Maintaining a balanced polarization of microglia is one of the most potential therapeutic approaches for diabetic retinopathy (DR). However, reliable, sustained, effective, and controllable microglial regulation still faces formidable challenges. Here, inspired by the bioavailability and modifiability of extracellular vesicles (EV), we developed an interleukin 4 (IL4)-encapsulated and M1 microglia-targeting EV platform (IL4@CHHSSSARC-EV) for rescuing inner blood-retina barrier (iBRB) deterioration in DR. Delivery of IL4 via IL4@CHHSSSARC-EV enhanced not only the stability of IL4, but also the efficacy of anti-inflammatory phenotype (M2) shift in vitro and in vivo due to their selectivity to pro-inflammatory (M1) microglia. Treatment with IL4@CHHSSSARC-EV significantly ameliorated pathologi

SUBMITTER: Fan Y 

PROVIDER: S-EPMC12860109 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature