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Record W4411620555 · doi:10.1038/s41467-025-60061-4

Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy

2025· article· en· W4411620555 on OpenAlexafffund
Gaël Cagnone, Sheetal Pundir, Charlotte Betus, Tapan Agnihotri, Anli Ren, Jin Sung Kim, Noémie-Rose Harvey, Émilie Heckel, Mei Xi Chen, Anu Situ, Perrine Gaub, Nicholas Kim, Ashim Das, Séverine Leclerc, Florian Wünnemann, Louis Berillon, Grégor Andelfinger, Sergio Crespo‐Garcia, Alexandre Dubrac, Flávio Rezende, Clary B. Clish, Bruno Maranda, José Carlos Rivera, Lois E. H. Smith, Przemysław Sapieha, Jean-Sébastien Joyal

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldMedicine
TopicRetinal Diseases and Treatments
Canadian institutionsMcGill UniversityHôpital Maisonneuve-RosemontNOSM UniversityUniversité de MontréalUniversité de SherbrookeCentre Hospitalier Universitaire Sainte-Justine
FundersFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentCentre hospitalier universitaire Sainte-JustineCentre de recherche du CHU Sainte-JustineCanadian Diabetes AssociationCanadian Institutes of Health ResearchMitacsGovernment of CanadaHeart and Stroke Foundation of Canada
KeywordsReprogrammingAngiogenesisNicheCancer researchNeovascularizationRegenerative medicineMedicineBiologyBioinformaticsCell biologyStem cellGeneticsCellBiochemistry

Abstract

fetched live from OpenAlex

Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization. Here we show that metabolic shifts in the neovascular niche define angiogenic fate. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological neovessels to a physiological phenotype, hastening vascular regeneration of the ischemic retina and improving vision. Hence, strategies to change the metabolic environment of vessels could promote a regenerative phenotype in vascular diseases. In proliferative retinopathies, pathological vessels replace healthy ones, impairing vision. Here, the authors show that reprogramming the metabolic environment of retinal blood vessels from fatty acid oxidation to glycolysis promotes healthy revascularization and improves vision in proliferative retinopathy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.325
Teacher spread0.310 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2025
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicRetinal Diseases and TreatmentsFrench-language works237,207