Evidence map›Paper›PMID 24425851›Full record

ArticleInvestigative ophthalmology & visual science2014

Targeting Müller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity.

Yanchao Jiang, Haibo Wang, David Culp, Zhihong Yang, Lori Fotheringham, John Flannery, Scott Hammond, Tal Kafri, M Elizabeth Hartnett

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.3field-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

36 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. The Role of Müller Cells in Diabetic Macular Edema.Investigative ophthalmology & visual science · 2023
    Review
  11. Systemic Cytokines in Retinopathy of Prematurity.Journal of personalized medicine · 2023
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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 at 3 institutions in 1 country.

Yanchao JiangDepartment of Ophthalmology, The John Moran Eye Center, University of Utah, Salt Lake City, Utah.
Haibo Wang
David Culp
Zhihong Yang
Lori Fotheringham
John Flannery
Scott Hammond
Tal Kafri
M Elizabeth Hartnett
University of Utah · USUniversity of North Carolina at Chapel Hill · USUniversity of California, Berkeley · US

Funding

University of Utah, Core Vision Research GrantP30EY014800 · NEI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Behrad Noudoost · 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
NEI NIH HHS P30 EY014800NEI NIH HHS R01 EY015130NEI NIH HHS R01EY015130NEI NIH HHS R01 EY017011NEI NIH HHS R01EY017011NIDDK NIH HHS R01 DK058702NIDDK NIH HHS R01-DK058702-10
6 · The paper itself

Abstract

purposeTo determine whether knockdown of Müller cell-derived VEGFA-splice variant, VEGF164, which is upregulated in the rat retinopathy of prematurity (ROP) model, safely inhibits intravitreal neovascularization (IVNV).

methodsShort hairpin RNAs for VEGF164 (VEGF164.shRNAs) or luciferase.shRNA control were cloned into lentivectors with CD44 promoters that specifically target Müller cells. Knockdown efficiency, off-target effects, and specificity were tested in HEK reporter cell lines that expressed green fluorescent protein (GFP)-tagged VEGF164 or VEGF120 with flow cytometry or in rat Müller cells (rMC-1) by real-time PCR. In the rat oxygen-induced retinopathy (OIR) ROP model, pups received 1 μL subretinal lentivector-driven luciferase.shRNA, VEGFA.shRNA, or VEGF164.shRNA at postnatal day 8 (P8). Analyses at P18 and P25 included: IVNV and avascular retina (AVA); retinal and serum VEGF (ELISA); density of phosphorylated VEGFR2 (p-VEGFR2) in lectin-labeled retinal endothelial cells (ECs; immunohistochemistry); TUNEL staining and thickness of inner nuclear (INL) and outer nuclear layers (ONL) in retinal cryosections; and pup weight gain.

resultsIn HEK reporter and in rMC-1 cells and in comparison to lucifferase.shRNA, VEGFA.shRNA reduced both VEGF120 and VEGF164, but VEGF164.shRNA only reduced VEGF164 and not VEGF120. Compared with luciferase.shRNA, VEGFA.shRNA and VEGF164.shRNA reduced retinal VEGF and IVNV without affecting AVA at P18 and P25. At P25, VEGF164.shRNA more effectively maintained IVNV inhibition than VEGFA.shRNA. VEGFA.shRNA and VEGF164.shRNA reduced pVEGFR2 in retinal ECs at P18, but VEGFA.shRNA increased it at P25. VEGFA.shRNA increased TUNEL+ cells at P18 and decreased ONL thickness at P18 and P25. VEGFA.shRNA and VEGF164.shRNA did not affect pup weight gain and serum VEGF.

conclusionsShort hairpin RNA to Müller cell VEGF164 maintained long-term inhibition of IVNV and limited cell death compared with shRNA to VEGFA.

Indexed as

Disease Models, AnimalMolecular Targeted TherapyAnimalsAnimals, NewbornEnzyme-Linked Immunosorbent AssayEpendymoglial CellsFlow CytometryGene Expression RegulationGene Knockdown TechniquesGenetic VectorsGreen Fluorescent ProteinsInjections, IntraocularRatsRats, Sprague-DawleyReal-Time Polymerase Chain ReactionRetinal NeovascularizationGreen Fluorescent ProteinsRNA, Small InterferingVascular Endothelial Growth Factor Avascular endothelial growth factor A, ratintravitreal neovascularizationlentivectorMüller cellsshort hairpin RNAvascular endothelial growth factor

Identifiers

PMID24425851
PMCPMC3920823
OpenAlexW2024173025

What OpenQuestion holds

Textmetadata
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.