Neurotoxic effects of dietary glutamate in glaucoma and potential nutritional and pharmacological therapies: a scoping review.

Authors

Larysse Maria Santiago de Castro, John Hebert da Silva Felix, Larissa Araújo Oliveira Alves, Maria Tayane Barroso Dos Santos, Antonio Átila Menezes Ferreira, Thiago Queiroz da Silva, José Cleiton Sousa Dos Santos, Aluísio Marques da Fonseca

Published in

International ophthalmology. Volume 46. Issue 1. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

To synthesize the available evidence on the relationship between dietary glutamate or glutamatergic metabolism and glaucomatous neurodegeneration, with emphasis on biomarkers, retinal injury mechanisms, and nutritional, antioxidant, or pharmacological strategies with neuroprotective potential.
This study was conducted as a systematic and bibliometric literature review following the PRISMA 2020 logic of identification, screening, eligibility, and inclusion. Searches were performed in Web of Science, Scopus, and PubMed for studies published in English between 2020 and 2025. The search strategy combined terms related to glaucoma or ocular neurodegeneration, the glutamatergic axis, and biomarkers, mechanisms, or interventions. After screening and full-text assessment, 39 studies were included in the systematic synthesis. Due to methodological heterogeneity, the evidence was synthesized narratively and comparatively, without meta-analysis.
The included studies were organized into six thematic clusters: metabolomic, transcriptomic, and diagnostic biomarkers; pharmacological and neuroprotective interventions; nutritional, antioxidant, and natural-compound neuroprotection; oxidative stress, mitochondrial dysfunction, and regulated cell death; neuroinflammation and glia-mediated retinal injury; and glutamatergic excitotoxicity and neurotransmitter imbalance. The evidence indicates that glutamate-related mechanisms in glaucoma are mainly associated with endogenous glutamatergic metabolism, excitotoxicity, impaired glutamate clearance, glutamate-glutamine homeostasis, oxidative and nitrosative stress, mitochondrial dysfunction, ferroptosis, neuroinflammation, and retinal ganglion cell vulnerability. None of the 39 included studies directly evaluated dietary glutamate or monosodium glutamate as the main exposure.
The available evidence does not support a direct conclusion that dietary glutamate or MSG intake contributes to glaucoma onset or progression. Instead, current findings mainly support an indirect mechanistic relationship between endogenous glutamatergic dysregulation and glaucomatous neurodegeneration. Pharmacological, antioxidant, metabolic, and natural-compound strategies show neuroprotective potential, particularly in experimental models, but clinical and translational studies are still needed to clarify the role of dietary exposure, glutamate-glutamine metabolism, and targeted neuroprotective interventions in glaucoma.

PMID:
42496936
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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