Identification of glutamine as a potential therapeutic target in dry eye disease.

Chen X, Zhang C, Peng F, Wu L, Zhuo D, Wang L, Zhang M, Li Z, Tian L, Jie Y, Huang Y, Yang X, Li X, Lei F, Cheng Y

Signal transduction and targeted therapy22 Jan 2025Cited by 19 (Europe PMC)

PMID39837870PMCIDPMC11751114DOI10.1038/s41392-024-02119-1PepBankPUB-39837870

Summary

Dry eye disease (DED) is a prevalent inflammatory condition significantly impacting quality of life, yet lacks effective pharmacological therapies. Herein, we proposed a novel approach to modulate the inflammation through metabolic remodeling, thus promoting dry eye recovery. Our study demonstrated that co-treatment with mesenchymal stem cells (MSCs) and thymosin beta-4 (Tβ4) yielded the best therapeutic outcome against dry eye, surpassing monotherapy outcomes. In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased glutamine levels in cornea following MSC + Tβ4 combined therapy. Inhibition of glutamine reversed the anti-inflammatory, anti-apoptotic, and homeostasis-preserving effects observed with combined therapy, highlighting the critical role of glutamine in dry eye therapy. Clinical cases and rodent model showed elevated expression of glutaminase (GLS1), an upstream enzyme in glutamine metabolism, following dry eye injury. Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced, respectively, the anti-inflammatory effects of combined therapy, underscoring GLS1's pivotal role in regulating glutamine metabolism. Furthermore, single-cell sequencing revealed a distinct subset of pro-inflammatory and pro-fibrotic corneal epithelial cells in the dry eye model, while glutamine treatment downregulated those subclusters, thereby reducing their inflammatory cytokine secretion. In summary, glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling. The present study suggests that glutamine metabolism plays a critical, previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

01AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Efficacy outcome
In dry eye models, co-treatment with MSCs and Tβ4 gave a better therapeutic outcome than monotherapy.
In plain wordsIn dry eye models, stem cells plus thymosin beta‑4 worked better than either one alone.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseDry eye therapeutic outcome
Study
n: not reported in source
Comparator
MSC alone or Tβ4 alone (monotherapy)
Outcome group
Ocular surface · Eye
Source sentences
Summary
Our study demonstrated that co-treatment with mesenchymal stem cells (MSCs) and thymosin beta-4 (Tβ4) yielded the best therapeutic outcome against dry eye, surpassing monotherapy outcomes.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3983787001
02AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In dry eye models, combined MSC and Tβ4 therapy increased glutamine levels in the cornea.
In plain wordsIn dry eye models, stem cells plus thymosin beta‑4 raised glutamine levels in the cornea.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseCorneal glutamine level
Study
n: not reported in source
Outcome group
Ocular surface · Eye
Source sentences
Summary
In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased glutamine levels in cornea following MSC + Tβ4 combined therapy.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3983787002
03AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In dry eye models, inhibition of glutamine reversed the anti-inflammatory, anti-apoptotic and homeostasis-preserving effects of combined MSC and Tβ4 therapy.
In plain wordsIn dry eye models, blocking glutamine removed the benefits of stem cells plus thymosin beta‑4.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseEffect of glutamine inhibition on combined therapy
Study
n: not reported in source
Outcome group
Ocular surface · Eye
Source sentences
Summary
Inhibition of glutamine reversed the anti-inflammatory, anti-apoptotic, and homeostasis-preserving effects observed with combined therapy, highlighting the critical role of glutamine in dry eye therapy.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3983787003
04AnimalNot a test of Thymosin beta-4 (human) aloneAnimal study (in vivo)Mechanism
In dry eye models, GLS1 overexpression counteracted and GLS1 inhibition enhanced the anti-inflammatory effects of combined MSC and Tβ4 therapy.
In plain wordsIn dry eye models, changing the enzyme GLS1 altered the anti-inflammatory effect of stem cells plus thymosin beta‑4.
Peptide
Thymosin beta-4 (human)
Outcome
MixedEffect of GLS1 modulation on combined therapy
Study
n: not reported in source
Outcome group
Ocular surface · Eye
Source sentences
Summary
Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced, respectively, the anti-inflammatory effects of combined therapy, underscoring GLS1's pivotal role in regulating glutamine metabolism.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3983787004

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

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