Prophylactic self-assembled nucleic acid hydrogel targeting retinal ganglion cell cuproptosis and microglial neuroinflammation for retinal ischemia-reperfusion injury.

ABSTRACT: Retinal ischemia-reperfusion (RIR) injury constitutes a common pathological pathway in glaucoma, diabetic retinopathy, and other neurodegenerative diseases, frequently leading to irreversible neuronal loss. This study identifies concurrent FDX1-dependent retinal ganglion cell (RGC) cuproptosis and MyD88-mediated microglial inflammation as key drivers of retinal neurodegeneration in RIR. To address this, we developed SAH-CIM, a self-assembled nucleic acid hydrogel for sustained co-delivery of siFdx1 and siMyd88. SAH-CIM effectively suppressed RGC cuproptosis via FDX1 knockdown and reduced pro-inflammatory cytokines by inhibiting the MyD88/TRAF6/NF-κB pathway. In murine RIR models, prophylactic SAH-CIM administration preserved 25.3% more retinal ganglion cells than free siRNA c

SUBMITTER: Liu S 

PROVIDER: S-EPMC12918180 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature