Tryptophan metabolism in glaucomatous optic neuropathy: from metabolic dysregulation to therapeutic opportunities

BACKGROUND: Glaucoma, a leading cause of irreversible blindness, involves progressive retinal ganglion cell loss. Beyond intraocular pressure, growing evidence implicates metabolic dysregulation as a key amplifying mechanism in glaucomatous damage. Among these metabolic changes, dysregulated tryptophan metabolism is increasingly recognized as a significant contributor to neurodegeneration. This review synthesizes clinical associations and preclinical mechanistic evidence linking tryptophan metabolism to glaucoma, discusses the potential underlying pathogenic mechanisms, and evaluates therapeutic strategies and research gaps. MAIN TEXT: Current evidence suggests that dysregulated tryptophan metabolism in glaucoma shifts the balance toward neurotoxic metabolites (e.g. quinolinic acid) and reduces protective ones (e.g. kynurenic acid, indole derivatives). These changes are linked to alterations in AhR-mediated immunomodulation, NMDAR excitotoxicity, oxidative stress, intraocular pressure and vascular regulation. Therapeutic interventions span enzyme modulation, receptor targeting, microbiome optimization, lifestyle adjustments, and metabolite supplementation. Clinical parallels from neurology offer proof-of-concept for translational potential, though challenges remain in bioavailability, patient stratification, and long-term adherence. CONCLUSIONS: Targeting tryptophan metabolism represents a promising, adjunctive strategy for neuroprotection in glaucoma. Future integration with multi-omics, biomarker development, and personalized medicine has the potential to shift glaucoma management from pressure-lowering to neuroprotection and metabolic restoration, providing a novel therapeutic framework for vision preservation.