Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: April 27, 2025
Abstract Retinal ischemia‐reperfusion (RIR) injury induces oxidative stress, excitotoxicity, inflammation, and ferroptosis, which interact through complex crosstalk, forming a retinal pathological microenvironment (RPMe) that drives ganglion cell (RGC) death. Central to these processes is the dysregulation of neuroimmune (NiMe), characterized by aberrant microglial activation around RGCs immune signaling imbalances. Here, analysis single‐cell RNA sequencing, it identifies significant sphingolipid pathway in RIR‐injured microglia, crosstalks with pathways. This crosstalk disrupts NiMe homeostasis. To address this, biomimetic nanoparticle system coated precursor membranes developed. co‐delivers CRISPR/Cas9‐based Acyl‐CoA synthetase long‐chain family member 4 (ACSL4) inhibitor suppress ferroptosis isorhamnetin, natural molecule identified directly bind protein kinase A inhibit glutamatergic synapse involved stress. By targeting its PI3K/AKT ASK1/JNK/NF‐κB pathways as well RGCs, this restores balance. The membrane‐coated offers novel, synergistic, targeted therapeutic strategy for RIR‐related diseases integrating CRISPR/Cas9 technology product therapy.
Language: Английский