Evidence map›Paper›PMID 39150511›Full record

ArticleActa diabetologica2025

Accumulation of branched-chain amino acids deteriorates the neuroinflammatory response of Müller cells in diabetic retinopathy via leucine/Sestrin2-mediated sensing of mTOR signaling.

Qiaoyun Gong, Jingyi Wang, Dawei Luo, Yupeng Xu, Rulin Zhang, Xin Li, Zihan Yin, Junwei Fang, Haiyan Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta diabetologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Qiaoyun GongDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jingyi WangDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Dawei LuoDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Yupeng XuDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Rulin ZhangDepartment of Laboratory Medicine, Shanghai General Hospital, Shanghai, China.
Xin LiDepartment of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Zihan YinDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Junwei FangDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Haiyan WangDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. hywang@sjtu.edu.cn.ORCID http://orcid.org/0000-0002-3770-5253

Funding

National Natural Science Foundation of China 81870666National Natural Science Foundation of China 82101132
6 · The paper itself

Abstract

aimsThis study aimed to investigate branched-chain amino acid (BCAA) catabolism in diabetic retinopathy (DR).

methodsWild-type and db/db mice were fed BCAAs (5 or 10 mg/kg/day) for 12 weeks, and hyperglycemia-exposed Müller cells were treated with BCAAs (2 or 5 mmol/L) for 24 and 48 h. BCAA levels were measured using MS/MS. Western blotting was performed to detect proteins. Flow cytometry, oxygen consumption rate, and Cell Counting Kit-8 assays were used to evaluate Müller cell viability. Each experiment was conducted at least thrice.

resultsBCAAs and branched-chain α-keto acids (BCKAs) were increased in the retina and systemic tissues of diabetic mice, and these changes were further enhanced to approximately 2-fold by extra BCAAs compared to wild-type group. In vitro, BCAAs and BCKAs were induced in hyperglycemic Müller cells, and augmented by BCAA supplementation. The aberrant BCAA catabolism was accompanied by mTORC1 activation and subsequently induced TNF-ɑ, VEGFA, GS, and GFAP in retinas and Müller cells under diabetic conditions. The cell apoptosis rate increased by approximately 50%, and mitochondrial respiration was inhibited by hyperglycemia and BCAA in Müller cells. Additionally, mTORC1 signaling was activated by leucine in Müller cells. Knockdown of Sestrin2 or LeuRS significantly abolished the leucine-induced mTORC1 phosphorylation and protected Müller cell viability under diabetic conditions.

conclusionsWe found that BCAA catabolism is hindered in DR through mTORC1 activation. Leucine plays a key role in inducing mTORC1 by sensing Sestrin2 in Müller cells. Targeting Sestrin2 may ameliorate the toxic effects of BCAA accumulation on Müller cells in DR.

Indexed as

Amino Acids, Branched-ChainDiabetic RetinopathyEpendymoglial CellsLeucineNeuroinflammatory DiseasesTOR Serine-Threonine KinasesAnimalsDiabetes Mellitus, ExperimentalMaleMiceMice, Inbred C57BLRetinaSignal TransductionAmino Acids, Branched-ChainLeucinemTOR protein, mouseTOR Serine-Threonine KinasesBranched-chain amino acidsDiabetic retinopathyGlialInflammationmTORC1

Identifiers

PMID39150511
PMCPMC11861416

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.