Evidence map›Paper›PMID 29730824›Full record

ArticleAngiogenesis2018

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy.

Aaron B Simmons, Colin A Bretz, Haibo Wang, Eric Kunz, Kassem Hajj, Carson Kennedy, Zhihong Yang, Thipparat Suwanmanee, Tal Kafri, M Elizabeth Hartnett

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Angiogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Aflibercept to treat retinopathy of prematurity: need for more research.Journal of perinatology : official journal of the California Perinatal Association · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
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  14. Review
  15. Article
  16. Review
  17. Pathophysiology of Retinopathy of Prematurity.Annual review of vision science · 2023
    Review
  18. Article
  19. Article
  20. Association between theOpen life sciences · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Aaron B SimmonsJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Colin A BretzJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Haibo WangJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Eric KunzJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Kassem HajjJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Carson KennedyJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Zhihong YangJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
Thipparat SuwanmaneeGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tal KafriGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
M Elizabeth HartnettJohn A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT, 84132, USA. ME.Hartnett@hsc.utah.edu.
University of Utah · USUniversity of North Carolina at Chapel Hill · US

Funding

University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI PAUL STEVEN BERNSTEIN · 2005 to 2026
$14.6M
Endothelial Transmigration in Neovascular Age-related Macular DegenerationR01EY017011 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HARTNETT, MARY ELIZABETH RUTH · 2007 to 2025
$7.7M
Mechanisms of Angiogenesis of Retinopathy of PrematurityR01EY015130 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mary Elizabeth Ruth Hartnett · 2005 to 2026
$7.6M
Nonintegrating Lentiviral Vectors Towards Clinical TrialsR01DK058702 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2001 to 2019
$5.0M
Lentiviral Vector-Based Gene Therapy and The Host Genetic BackgroundR01HL128119 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2015 to 2018
$3.0M
Vision Research Training Grant at the University of UtahT32EY024234 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI DAVID KRIZAJ, Monica L Vetter · 2014 to 2026
$2.3M
Mechanisms of Angiogenesis in Retinopathy of PrematurityR56EY015130 · NEI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HARTNETT, MARY ELIZABETH RUTH · 2009 to 2009
$370k
Episomal lenti vector for a humanized hemophilia mouseR56DK058702 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2006 to 2006
$75k
NEI NIH HHS EY014800NEI NIH HHS EY015130NEI NIH HHS EY017011NEI NIH HHS EY024234NEI NIH HHS P30 EY014800NEI NIH HHS R01 EY015130NEI NIH HHS R01 EY017011NEI NIH HHS R56 EY015130NEI NIH HHS T32 EY024234NHLBI NIH HHS HL128119NHLBI NIH HHS R01 HL128119NIDDK NIH HHS DK058702NIDDK NIH HHS R01 DK058702NIDDK NIH HHS R56 DK058702
6 · The paper itself

Abstract

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

Indexed as

AnimalsEndothelial CellsGene Knockdown TechniquesGenetic TherapyGenetic VectorsLentivirusRatsRats, Sprague-DawleyRetinal NeovascularizationRetinal VesselsSTAT3 Transcription FactorVascular Endothelial Growth Factor Receptor-2Kdr protein, ratStat3 protein, ratSTAT3 Transcription FactorVascular Endothelial Growth Factor Receptor-2Age-related macular degenerationAnti-VEGFBevacizumabDiabetic retinopathyRanibizumabRetinopathy of prematurity

Identifiers

PMID29730824
PMCPMC6203654
OpenAlexW2801340054

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.