Evidence map›Paper›PMID 31449794›Full record

ArticleExperimental eye research2019

Angiotensin receptor expression revealed by reporter mice and beneficial effects of AT2R agonist in retinal cells.

Amrisha Verma, Ping Zhu, Annette de Kloet, Eric Krause, Colin Sumners, Qiuhong Li

Abstract read
In one paragraph

Article in Experimental eye research, 2019. 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.

  1. Review
  2. The Angiotensin ATPharmacological reviews · 2022
    Review
  3. Article
  4. Review
  5. Review
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

6 authors.

Amrisha VermaDepartments of Ophthalmology, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Ping ZhuDepartments of Ophthalmology, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Annette de KloetPhysiology & Functional Genomics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Eric KrauseCollege of Medicine, Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Colin SumnersPhysiology & Functional Genomics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA.
Qiuhong LiDepartments of Ophthalmology, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA. Electronic address: qli@ufl.edu.

Funding

Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Oral therapy for diabetic retinopathy using ACE2/Ang1-7 bioencapsulated in plant cellsR01EY024564 · NEI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, LI, QIUHONG · 2015 to 2018
$1.6M
Ocular Renin Angiotensin System in Pathogenesis of Diabetic RetinopathyR01EY021752 · NEI · UNIVERSITY OF FLORIDA · PI LI, QIUHONG · 2012 to 2015
$1.4M
NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY021752NEI NIH HHS R01 EY024564
6 · The paper itself

Abstract

The renin-angiotensin system (RAS) plays a vital role in cardiovascular physiology and body homeostasis. In addition to circulating RAS, a local RAS exists in the retina. Dysfunction of local RAS, resulting in increased levels of Angiotensin II (Ang II) and activation of AT1R-mediated signaling pathways, contributes to tissue pathophysiology and end-organ damage. Activation of AT2R on other hand is known to counteract the effects of AT1R activation and produce anti-inflammatory and anti-oxidative effects. We examined the expression of angiotensin receptors in the retina by using transgenic dual reporter mice and by real-time RT-PCR. We further evaluated the effects of C21, a selective agonist of AT2R, in reducing Ang II, lipopolysaccharide (LPS) and hydrogen peroxide induced oxidative stress and inflammatory responses in cultured human ARPE-19 cells. We showed that both AT1Ra and AT2R positive cells are detected in different cell types of the eye, including the RPE/choroid complex, ciliary body/iris, and neural retina. AT1Ra is more abundantly expressed than AT2R in mouse retina, consistent with previous reports. In the neural retina, AT1Ra are also detected in photoreceptors whereas AT2R are mostly expressed in the inner retinal neurons and RGCs. In cultured human RPE cells, activation of AT2R with C21 significantly blocked Ang II, LPS and hydrogen peroxide -induced NF-κB activation and inflammatory cytokine expression; Ang II and hydrogen peroxide-induced reactive oxygen species (ROS) production and MG132-induced apoptosis, comparable to the effects of Angiotensin-(1-7) (Ang-(1-7)), another protective component of the RAS, although C21 is more potent in reducing some of the effects induced by Ang II, whereas Ang-(1-7) is more effective in reducing some of the LPS and hydrogen peroxide-induced effects. These results suggest that activation of AT2R may represent a new therapeutic approach for retinal diseases.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCells, CulturedCell SurvivalCytokinesGene Expression RegulationHumansMiceMice, Inbred C57BLMice, TransgenicNF-kappa BReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionReceptor, Angiotensin, Type 2Receptors, AngiotensinRenin-Angiotensin SystemAdaptor Proteins, Signal TransducingAgtrap protein, mouseCytokinesN-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamideNF-kappa BReactive Oxygen SpeciesReceptor, Angiotensin, Type 2Receptors, AngiotensinRNA, MessengerSulfonamidesThiophenesAngiotensin IIAT2RC21Renin angiotensin systemRetina

Identifiers

PMID31449794
PMCPMC6759374

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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 OpenQuestion graph.