Evidence map›Paper›PMID 30092004›Full record

ArticlePloS one2018

Differential effects of angiotensin II type I receptor blockers on reducing intraocular pressure and TGFβ signaling in the mouse retina.

Ralph J Hazlewood, Qingxia Chen, Frances K Clark, John Kuchtey, Rachel W Kuchtey

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

14 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  5. Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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  7. Optic neuropathy associated with TGFβ dysregulation in mice with a glaucoma-causative mutation of ADAMTS10.Matrix biology : journal of the International Society for Matrix Biology · 2022
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  14. Telmisartan Reduces Axon Degeneration in Mice With Experimental Glaucoma.Investigative ophthalmology & visual science · 2020
    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

5 authors at 2 institutions in 1 country.

Ralph J HazlewoodDepartment of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Qingxia ChenDepartment of Biostatistics, Vanderbilt University, Nashville, TN, United States of America.
Frances K ClarkDepartment of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
John KuchteyDepartment of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Rachel W KuchteyDepartment of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Vanderbilt University Medical Center · USVanderbilt University · US

Funding

Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 1989 to 2026
$19.6M
Targeting Tissue Biomechanics for Treatment of GlaucomaR01EY020894 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KUCHTEY, RACHEL W · 2010 to 2025
$6.4M
NEI NIH HHS P30 EY008126NEI NIH HHS R01 EY020894
6 · The paper itself

Abstract

purposeAngiotensin II type 1 receptor blockers (ARBs) have been investigated for their neuroprotective and intraocular pressure (IOP) lowering effects in treating glaucoma, but the reports have been inconsistent possibly because different compounds and models have been used. Here we selected three ARBs for head-to-head comparisons of their effects on IOP and transforming growth factor β (TGFβ) signaling, which is believed to play an important role in glaucoma pathogenesis.

methodsThree ARBs (losartan, irbesartan or telmisartan) or vehicle controls were administered via chow to C57BL/6J mice for up to 7 days. Drug concentrations in the eye, brain, and plasma were evaluated by liquid chromatography mass spectrometry. Cohorts of mice were randomly assigned to different treatments. IOP and blood pressure were measured before and after ARB treatment. Effects of ARBs on TGFβ signaling in the retina were evaluated by phosphorylated Smad2 (pSmad2) immunohistochemistry.

resultsPhysiologically relevant concentrations of losartan, irbesartan and telmisartan were detected in eye, brain and plasma after drug administration (n = 11 mice/treatment). Blood pressure was significantly reduced by all ARBs compared to vehicle-fed controls (all p-values < 0.001, n = 8-15 mice/treatment). Compared to vehicle control, IOP was significantly reduced by irbesartan (p = 0.030) and telmisartan (p = 0.019), but not by losartan (n = 14-17 mice/treatment). Constitutive pSmad2 fluorescence observed in retinal ganglion cells was significantly reduced by telmisartan (p = 0.034), but not by losartan or irbesartan (n = 3-4 mice/treatment).

conclusionsAdministration via chow is an effective delivery method for ARBs, as evidenced by lowered blood pressure. ARBs vary in their abilities to lower IOP or reduce TGFβ signaling. Considering the significant roles of IOP and TGFβ in glaucoma pathogenesis, specific ARBs with dual effects, such as telmisartan, may be more effective than other ARBs for treating glaucoma.

Indexed as

Angiotensin II Type 1 Receptor BlockersAnimalsBlood PressureIntraocular PressureMaleMiceMice, Inbred C57BLPhosphoproteinsRetinaSignal TransductionSmad2 ProteinTransforming Growth Factor betaAngiotensin II Type 1 Receptor BlockersPhosphoproteinsSmad2 ProteinTransforming Growth Factor beta

Identifiers

PMID30092004
PMCPMC6084929
OpenAlexW2886216285

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.