Beyond antioxidation: Retinal neuroprotection by Lycium barbarum polysaccharides via multiple signaling pathways

Age-related macular degeneration, glaucoma, retinitis pigmentosa, and diabetic retinopathy are the major retinal degenerative disorders, and each ultimately leads to irreversible vision loss. In this context, single-target therapies aimed at isolated pathways have delivered only modest benefits. Lycium barbarum polysaccharides, the predominant bioactive components of goji berries, emerge as far more than simple antioxidants, functioning instead as orchestrators of interconnected signaling networks. Growing evidence shows that Lycium barbarum polysaccharides engages pathways well beyond redox control to interrupt disease-driving cascades: it limits cellular senescence through the SIRT1/p53 axis, preserves blood-retinal barrier integrity by maintaining aquaporin-4 at astrocytic endfeet, and biases microglia from proinflammatory M1 toward reparative M2 states. Beyond immunomodulation, Lycium barbarum polysaccharides promotes clearance of pathogenic protein aggregates and suppresses pathological neovascularization via the miR-15a-5p/ VEGFR2 axis. While antioxidant effects may predominate in early disease, the actions of LBP become more targeted as pathology advances, a stage-dependent selectivity that helps explain its cross-disease efficacy. In age-related macular degeneration, Lycium barbarum polysaccharides sustains metabolic homeostasis in retinal pigment epithelium by tuning autophagic flux through the miR-181/BCL-2 axis. In glaucoma, it safeguards mitochondrial membrane potential in retinal ganglion cells, supporting energy metabolism and survival. Collectively, these properties position Lycium barbarum polysaccharides as a pleiotropic regulator capable of reshaping multiple disease trajectories. Realizing its clinical potential will require precise identification of active metabolites, rigorous in vivo pharmacokinetic profiling, and rational combination with current standard-of-care therapies.