Stage-specific nanotherapeutics for glaucoma target elevated IOP, impaired aqueous-humor outflow, RGC degeneration, and fibrotic inflammation during postoperative wound healing

Abstract

Glaucoma is a chronic neurodegenerative disease in which elevated intraocular pressure (IOP), impaired aqueous-humor outflow, retinal ganglion cell (RGC) degeneration, and postoperative fibrosis may coexist or predominate at different stages. Conventional therapies are effective in many patients, but important limitations remain: topical eye drops have short ocular residence times and depend on long-term adherence, IOP reduction does not fully prevent neurodegeneration, and postoperative wound healing can compromise the success of filtration surgery. Nanomedicine provides an opportunity to align therapeutic cargo, administration route, tissue target, and duration of exposure with these distinct clinical needs. To provide a clinically oriented framework for this broad field, we organize the review by therapeutic compartment and clinical decision point rather than by nanomaterial class. We first examine nanoenabled topical, injectable, and implantable systems for durable IOP control, followed by strategies targeting the trabecular meshwork (TM) and Schlemm’s canal (SC) to restore conventional aqueous-humor outflow. We next evaluate antioxidant, neurotrophic, extracellular-vesicle, nucleic-acid, and stimulus-responsive strategies for RGC protection and regeneration, followed by local nanomaterial approaches designed to modulate postoperative inflammation and fibrosis. Across these applications, the most compelling advances are those in which the material addresses a clearly defined therapeutic or delivery limitation without introducing unnecessary complexity. Major translational barriers nevertheless remain, including cumulative ocular exposure, material degradation and clearance, corneal endothelial and retinal safety, immunogenicity, batch-to-batch reproducibility, aseptic manufacturing, sterilization compatibility, storage stability, scale-dependent release kinetics, and regulatory requirements for drug–device combination products. Future development should prioritize degradable or retrievable systems, clinically relevant chronic disease models, prespecified critical quality attributes, scalable manufacturing processes, and outcome measures that integrate IOP control with structural preservation, functional benefit, and patient experience. A stage- and compartment-specific framework may therefore help shift glaucoma nanomedicine from a broad catalogue of materials toward focused, testable, and clinically translatable therapeutic strategies.