Evidence map›Paper›PMID 26529046›Full record

ArticleInvestigative ophthalmology & visual science2015

Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice.

Takeshi Mizutani, Benjamin J Fowler, Younghee Kim, Reo Yasuma, Laura A Krueger, Bradley D Gelfand, Jayakrishna Ambati

Open access · hybridAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
4.0field-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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Voluntary Exercise Suppresses Choroidal Neovascularization in Mice.Investigative ophthalmology & visual science · 2020
    Article
  14. Attenuating Diabetic Vascular and Neuronal Defects by Targeting P2rx7.International journal of molecular sciences · 2019
    Article
  15. Article
  16. Pleiotropic Roles of P2X7 in the Central Nervous System.Frontiers in cellular neuroscience · 2019
    Review
  17. Review
  18. Review
  19. New Therapies of Neovascular AMD-Beyond Anti-VEGFs.Vision (Basel, Switzerland) · 2018
    Review
  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

7 authors at 1 institution in 1 country.

Takeshi MizutaniDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States.
Benjamin J FowlerDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States.
Younghee KimDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States.
Reo YasumaDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States.
Laura A KruegerDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States.
Bradley D GelfandDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States 2Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, United States 3Department of Microbiology, Immunology, and Mole.
Jayakrishna AmbatiDepartment of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States 4Department of Physiology, University of Kentucky, Lexington, Kentucky, United States.
University of Kentucky · US

Funding

Form and function of our Janus faced genomeDP1GM114862 · NIGMS · UNIVERSITY OF VIRGINIA · PI AMBATI, JAYAKRISHNA · 2014 to 2018
$4.0M
KENTUCKY CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCEUL1RR033173 · NCRR · UNIVERSITY OF KENTUCKY · PI KERN, PHILIP A · 2011 to 2011
$3.5M
Functional studies of DICER1 and Alu RNA in geographic atrophyR01EY022238 · NEI · UNIVERSITY OF VIRGINIA · PI AMBATI, JAYAKRISHNA · 2012 to 2016
$3.3M
Inflammasome Activation in Geographic AtrophyR01EY024068 · NEI · UNIVERSITY OF VIRGINIA · PI AMBATI, JAYAKRISHNA · 2014 to 2017
$2.6M
Clinical Scholars In Cardiovascular ScienceT32HL091812 · NHLBI · UNIVERSITY OF KENTUCKY · PI SMYTH, SUSAN S. · 2008 to 2018
$2.3M
Pro-and anti-angiogenic effects of vascular endothelial growth factor-AR01EY018350 · NEI · UNIVERSITY OF KENTUCKY · PI AMBATI, JAYAKRISHNA · 2007 to 2011
$1.9M
Intrinsic anti-angiogenic activity of siRNAR01EY018836 · NEI · UNIVERSITY OF KENTUCKY · PI AMBATI, JAYAKRISHNA · 2008 to 2011
$1.9M
Endogenous Specific Inhibitor of Corneal LymphangiogenesisR01EY020672 · NEI · UNIVERSITY OF KENTUCKY · PI AMBATI, JAYAKRISHNA · 2010 to 2013
$1.5M
NCCDPHP CDC HHS DP1GM114862NCRR NIH HHS UL1 RR033173NCRR NIH HHS UL1RR033173NEI NIH HHS R01 EY018350NEI NIH HHS R01EY018350NEI NIH HHS R01 EY018836NEI NIH HHS R01EY018836NEI NIH HHS R01 EY020672NEI NIH HHS R01EY020672NEI NIH HHS R01 EY022238NEI NIH HHS R01EY022238NEI NIH HHS R01 EY024068NEI NIH HHS R01EY024068NHLBI NIH HHS T32 HL091812NHLBI NIH HHS T32HL091812NIGMS NIH HHS DP1 GM114862
6 · The paper itself

Abstract

purposeTo evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV).

methodsWe evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3-/-, and P2rx7-/- mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2', 3'-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA.

resultsIntravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3-/- mice (P < 0.05) but not in P2rx7-/- mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7-/- mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC.

conclusionsMultiple clinically relevant NRTIs suppressed laser-induced CNV and downregulated VEGF-A, via P2X7.

Indexed as

AnimalsChoroidal NeovascularizationDisease Models, AnimalEnzyme-Linked Immunosorbent AssayEye ProteinsFluorescein AngiographyFundus OculiHEK293 CellsHumansIntravitreal InjectionsLasersMiceMice, Inbred C57BLMicroscopy, ConfocalReverse Transcriptase InhibitorsEye ProteinsReverse Transcriptase Inhibitors

Identifiers

PMID26529046
PMCPMC4634627
OpenAlexW2337730099

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.