Lycium Barbarum Polysaccharide‐Derived Nanoparticles Protect Visual Function by Inhibiting RGC Ferroptosis and Microglial Activation in Retinal Ischemia‒Reperfusion Mice

Abstract Retinal ischemia‒reperfusion (IR) is a major contributor to vision impairment and irreversible vision loss due to retinal ganglion cell (RGC) injury or loss. Contemporary therapeutic approaches predominantly focus on the amelioration of symptoms rather than addressing the fundamental etiological factors. Oxidative stress is a notable feature and an important mediator of IR damage. Lycium barbarum polysaccharide (LBP), the main active ingredient of Lycium barbarum, has various pharmacological effects, including antioxidation, immunoregulation, and neuroprotective effects. In this study, the ROS‐consumable moiety phenylboronic acid pinacol ester (PBA) is introduced to LBP molecules, which can self‐assemble into nanoparticles in aqueous solution. This nanoparticle (termed PLBP) can reduce the cellular ROS levels and enhance the antioxidant capability of RGCs by activating the NRF2 pathway, thus protecting RGCs from ferroptosis and preserving visual function in response to IR injury. PLBP also reduces neuroinflammation by inhibiting the ability of microglia to phagocytose, migrate, secrete inflammatory cytokines, and activate the NF‐κB pathway. In conclusion, this approach can be used as an inspiration for the future development of neuroprotective drugs.