Evidence map›Paper›PMID 33099660›Full record

ArticleDiabetologia2021

Vitreous metabolomics profiling of proliferative diabetic retinopathy.

Yohei Tomita, Gael Cagnone, Zhongjie Fu, Bertan Cakir, Yumi Kotoda, Masaki Asakage, Yoshihiro Wakabayashi, Ann Hellström, Jean-Sébastien Joyal, Saswata Talukdar and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
7.6field-weighted citation impact, top 2% of its field
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

50 citing papers in PubMed, 82 citations in OpenAlex.

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  9. Single-cell analysis identifies MKI67Journal of translational medicine · 2025
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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

12 authors at 6 institutions in 4 countries.

Yohei TomitaDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1013-5737
Gael CagnoneDepartment of Pediatrics, Pharmacology and Ophthalmology, CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
Zhongjie FuDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Bertan CakirDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Yumi KotodaDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Masaki AsakageDepartment of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan.
Yoshihiro WakabayashiDepartment of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan.
Ann HellströmPediatric Ophthalmology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Jean-Sébastien JoyalDepartment of Pediatrics, Pharmacology and Ophthalmology, CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada.
Saswata TalukdarMerck & Co., Inc., South San Francisco, CA, USA.
Lois E H SmithDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Lois.Smith@childrens.harvard.edu.ORCID 0000-0001-7644-6410
Yoshihiko UsuiDepartment of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan. usuyoshi@gmail.com.ORCID 0000-0002-1258-3587
Boston Children's Hospital · USCentre Hospitalier Universitaire Sainte-Justine · CATokyo Medical University Hospital · JPMerck & Co., Inc., Rahway, NJ, USA (United States) · USTokyo Medical University · JPUniversity of Gothenburg · SE

Funding

Dietary control of angiogenesis in retinopathy modelsR01EY017017 · NEI · BOSTON CHILDREN'S HOSPITAL · PI Zhongjie Fu, Lois Smith · 2006 to 2026
$11.8M
Novel therapies to inhibit Diabetic RetinopathyR24EY024864 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KERN, TIMOTHY S · 2015 to 2019
$8.1M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2M
Glucose/lipid metabolism and vessel development in phase I ROPR01EY030904 · NEI · BOSTON CHILDREN'S HOSPITAL · PI SMITH, LOIS · 2020 to 2023
$1.7M
BLR&D Research Career Scientist ApplicationIK6BX003604 · VA · VETERANS HEALTH ADMINISTRATION · PI KERN, TIMOTHY S · 2017 to 2021
–
BLRD VA IK6 BX003604Canadian Institute of Health Research 390615NEI NIH HHS R01 EY017017NEI NIH HHS R01 EY030904NEI NIH HHS R24 EY024864NICHD NIH HHS U54 HD090255NIH HHS R24EY024868the Ministry of Education, Culture, Sports, Science and Technology of Japan 19K09959the Natural Sciences and Engineering Research Council of Canada RGPIN-2016-06743
6 · The paper itself

Abstract

aims/hypothesisProliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR.

methodsWe analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration.

resultsWe identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/

interpretationThese results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.

Indexed as

MetabolomicsAdultAgedAged, 80 and overAmino AcidsAnimalsChromatography, High Pressure LiquidCreatineDiabetic RetinopathyFemaleHumansMaleMass SpectrometryMiceMice, Inbred C57BLMiddle AgedAmino AcidsCreatineCreatineMetabolomicsOxygen-induced retinopathyProliferative diabetic retinopathyRetinal neovascularisation

Identifiers

PMID33099660
PMCPMC7718434
OpenAlexW3094247546

What OpenQuestion holds

Textmetadata
LicenceTDM
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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 OpenQuestion graph.