Evidence mapPaperPMID 40970668Full record

ArticleInvestigative ophthalmology & visual science2025

Endothelial-Pericyte Interactions Regulate Angiogenesis Via VEGFR2 Signaling During Retinal Development and Disease.

Ying-Yu Lin, Emily Warren, Bria L Macklin, Lucas Ramirez, Sharon Gerecht

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Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Ying-Yu LinDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
Emily WarrenDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
Bria L MacklinDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States.
Lucas RamirezDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
Sharon GerechtDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, United States.

Funding

Women's Cancer ProgramP30CA014236 · NCI · DUKE UNIVERSITY · 1985 to 2025
$66.3M
Engineering three-dimensional perfusable microphysiological models of the human inner blood-retina barrierR01EY035853 · DUKE UNIVERSITY · 2025 to 2025
$603k
NCI NIH HHS P30 CA014236NEI NIH HHS R01 EY035853NHLBI NIH HHS F31 HL143972
6 · The paper itself

Abstract

Purpose: Endothelial-pericyte interaction disruption causes vascular dropout and pathological angiogenesis, severely impacting visual function in ocular microvascular diseases. This study examines VEGF receptor 2 (VEGFR2) signaling in endothelial-pericyte interactions, highlighting VEGFR2 as a potential therapeutic target for promoting pericyte coverage and decreasing vascular leakage in diseased retinas. Method: Cell-cell interactions with VEGFR2 signaling were assessed using isogenic endothelial cells and pericytes from induced pluripotent stem cells. We investigated changes in VEGFR2 signaling resulting from endothelial-pericyte interactions using quantitative Reverse Transcription PCR, western blot analysis, immunofluorescence staining, migration assays, permeability assays, transendothelial electrical resistance measurements, flow cytometry, and three-dimensional collagen gel vascular networks. We validated VEGFR2 as a therapeutic target via intravitreal injection in the oxygen-induced retinopathy mouse model. Treatment effects were evaluated using western blot analysis, immunofluorescence staining, and an FITC-dextran permeability assay to assess protein expression, pericyte recruitment, and retinal vascular function in response to VEGFR2 modulation. Results: We demonstrate that direct endothelial-pericyte contact, mediated by N-cadherin, downregulates phosphorylated VEGFR2 in endothelial cells, thereby enhancing pericyte migration and promoting endothelial cell barrier function. Intravitreal injection of a VEGFR2 inhibitor in mouse models of the developing retina and oxygen-induced retinopathy increased pericyte recruitment and decreased vascular leakage. The VEGFR2 inhibitor further rescued ischemic retinopathy by enhancing vascularization and tissue growth. Conclusions: Our findings uncover a novel mechanism by which VEGFR2 signaling is regulated through endothelial-pericyte interactions, promoting pericyte migration and strengthening endothelial barrier function. These results suggest a pathway that could be harnessed to support the growth of functional and mature microvasculature in ocular microvascular diseases and tissue regeneration overall.

Indexed as

Endothelial CellsEndothelium, VascularPericytesRetinaRetinal NeovascularizationVascular Endothelial Growth Factor Receptor-2AngiogenesisAnimalsBlotting, WesternCell CommunicationCell MovementCells, CulturedDisease Models, AnimalFlow CytometryHumansIntravitreal InjectionsKdr protein, mouseVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID40970668
PMCPMC12453065

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.