# Metabolomic Analysis of Aqueous Humor to Predict Glaucoma Progression and Overall Survival After Glaucoma Surgery—The MISO II Study

**Authors:** Laurens Detremmerie, Anca Croitor Sava, Uwe Himmelreich, Ingeborg Stalmans, Jan Van Eijgen, João Barbosa-Breda

PMC · DOI: 10.3390/metabo16020100 · Metabolites · 2026-01-29

## TL;DR

This study explores how the chemical makeup of eye fluid can predict glaucoma progression and survival after surgery.

## Contribution

The study identifies specific metabolites in aqueous humor that predict glaucoma progression and mortality after surgery.

## Key findings

- Glutamine and α-ketoglutarate are linked to glaucoma progression.
- N-acetylglutamate, lysine, and creatine correlate with mortality after surgery.
- These metabolites suggest roles in excitotoxicity and mitochondrial dysfunction in glaucoma.

## Abstract

Background/Objectives: Although advances in understanding glaucoma have been made, early detection remains challenging due to the asymptomatic nature of the disease. The Metabolomics In Surgical Ophthalmological Patients (MISO) study previously demonstrated that aqueous humor (AH) metabolomics can distinguish glaucoma patients from controls. We aimed to determine if the metabolic profile of AH has predictive power for overall survival and glaucoma progression after surgery. Methods: Glaucoma patients (n = 34) were retrospectively analyzed and classified into progression categories based on surgical and medical interventions and assessed for survival. Results: Glutamine and α-ketoglutarate were significantly associated with glaucoma progression, while N-acetylglutamate, lysine, and creatine correlated with mortality. These metabolites are linked to excitotoxicity, mitochondrial dysfunction, and oxidative stress, highlighting their potential role in glaucoma pathophysiology. Conclusions: These results suggest that metabolomic profiling of AH could provide valuable biomarkers for predicting surgical outcomes and overall survival, paving the way for individualized therapeutic approaches. Further studies are required to confirm these findings before they can be integrated into clinical practice.

## Linked entities

- **Chemicals:** glutamine (PubChem CID 738), N-acetylglutamate (PubChem CID 70914), lysine (PubChem CID 866), creatine (PubChem CID 586)
- **Diseases:** glaucoma (MONDO:0005041)

## Full-text entities

- **Genes:** Slc1a2 (solute carrier family 1 (glial high affinity glutamate transporter), member 2) [NCBI Gene 20511] {aka 1700091C19Rik, 2900019G14Rik, Eaat2, GLT-1, GLT1, MGLT1}, GLUL (glutamate-ammonia ligase) [NCBI Gene 2752] {aka DEE116, GLNS, GS, PIG43, PIG59}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, CAT (catalase) [NCBI Gene 847], PAG1 (phosphoprotein membrane anchor with glycosphingolipid microdomains 1) [NCBI Gene 55824] {aka CBP, PAG}, GLS2 (glutaminase 2) [NCBI Gene 27165] {aka GA, GLS, LGA, hLGA}, SLC1A3 (solute carrier family 1 member 3) [NCBI Gene 6507] {aka EA6, EAAT1, GLAST, GLAST1}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, Slc38a3 (solute carrier family 38, member 3) [NCBI Gene 76257] {aka 0610012J02Rik, D9Ucla2, Nat1, Slc38-3, Sn1, Snat3}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** visual field defects (MESH:D005128), ganglion (MESH:D045888), glaucomatous neuropathy (MESH:D009422), ocular hypertension (MESH:D009798), neuronal death (MESH:D009410), cataract (MESH:D002386), coronary, cerebrovascular, and arterial occlusive diseases (MESH:D003324), Glaucoma (MESH:D005901), RGC (MESH:D012173), AH (MESH:C562390), NTG (OMIM:606657), dehydration (MESH:D003681), ALS (MESH:D000690), retinal vein occlusion (MESH:D012170), death (MESH:D003643), POAG (MESH:D005902), vascular dysregulation (MESH:D021081), blindness (MESH:D001766), diabetes mellitus (MESH:D003920), HD (MESH:D006816), Metabolic and Vascular Disease (MESH:D014652), neurotoxicity (MESH:D020258), AD (MESH:D000544), myopia (MESH:D009216), neuroinflammation (MESH:D000090862), MISO (MESH:D007431), normal tension glaucoma (MESH:D057066), optic neuropathy (MESH:D009901), inflammatory (MESH:D007249), neurodegenerative diseases (MESH:D019636), injury to (MESH:D014947), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** lysine (MESH:D008239), calcium (MESH:D002118), ROS (MESH:D017382), PGA (MESH:D011454), glucose (MESH:D005947), creatinine (MESH:D003404), D-Glutamine (MESH:D005973), ATP (MESH:D000255), thiamine (MESH:D013831), CAI (MESH:C062058), arginine (MESH:D001120), phosphocreatine (MESH:D010725), Cr (MESH:D003401), AA (-), aminoacyl-tRNA (MESH:D012346), hydroxyproline (MESH:D006909), alpha-ketoglutarate (MESH:D007656), D-glutamate (MESH:D018698), N-acetylglutamate (MESH:C016195), NMDA (MESH:D016202), galactose (MESH:D005690), glycine (MESH:D005998), glyoxylate (MESH:C031150), sodium azide (MESH:D019810), nicotinamide (MESH:D009536), tyrosine (MESH:D014443), prostaglandin (MESH:D011453), alanine (MESH:D000409), tricarboxylic acid (MESH:D014233), Agmatine (MESH:D000376), proline (MESH:D011392), Methionine (MESH:D008715), oxygen (MESH:D010100), acid (MESH:D000143)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** Glutamine-Glutamate, glutamate with the lysine, AUC of 0, glutamate is converted to glutamine

## Full text

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## Figures

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## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943261/full.md

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Source: https://tomesphere.com/paper/PMC12943261