Evidence map›Paper›PMID 21357408›Full record

ArticleInvestigative ophthalmology & visual science2011

Expression and iron-dependent regulation of succinate receptor GPR91 in retinal pigment epithelium.

Jaya P Gnana-Prakasam, Sudha Ananth, Puttur D Prasad, Ming Zhang, Sally S Atherton, Pamela M Martin, Sylvia B Smith, Vadivel Ganapathy

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.0field-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

33 citing papers in PubMed, 57 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Jaya P Gnana-PrakasamDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Sudha Ananth
Puttur D Prasad
Ming Zhang
Sally S Atherton
Pamela M Martin
Sylvia B Smith
Vadivel Ganapathy
Augusta University · US

Funding

Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.R01EY014560 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI SMITH, SYLVIA B. · 2004 to 2013
$2.7M
Retinal Iron Homeostasis in Health and DiseaseR01EY019672 · NEI · AUGUSTA UNIVERSITY · PI GANAPATHY, VADIVEL · 2010 to 2013
$1.4M
NEI NIH HHS EY019672NEI NIH HHS R01 EY014560NEI NIH HHS R01 EY019672
6 · The paper itself

Abstract

purposeGPR91, a succinate receptor, is expressed in retinal ganglion cells and induces vascular endothelial growth factor (VEGF) expression. RPE also expresses VEGF, but whether this cell expresses GPR91 is not known. Excessive iron is also proangiogenic, and hemochromatosis is associated with iron overload. Therefore, we examined the expression and iron-dependent regulation of GPR91 in the RPE.

methodsGPR91 expression was examined by RT-PCR and immunohistochemistry. Hemochromatosis mice, cytomegalovirus (CMV) infection of retina, expression of CMV-US2 in RPE, and exposure of RPE to ferric ammonium citrate (FAC) were used to examine the iron-dependent regulation of GPR91 expression. VEGF expression was quantified by qPCR. Knockdown of GPR91 in ARPE-19 cells was achieved with shRNA.

resultsGPR91 was expressed in RPE but only in the apical membrane. Retinal expression of GPR91 was higher in hemochromatosis (Hfe(-/-)) mice than in wild-type (WT) mice. Primary RPE cells from Hfe(-/-) mice had increased GPR91 expression compared with WT RPE cells. Iron accumulation in cells induced by CMV infection, expression of CMV-US2, or treatment with FAC increased GPR91 expression. VEGF expression in the Hfe(-/-) mouse retina was increased at ages younger than 18 months, but the expression was downregulated at older ages. The involvement of GPR91 in succinate-induced expression of VEGF in RPE cells was confirmed with GPR91-specific shRNA.

conclusionsGPR91 is expressed in the RPE with specific localization to the apical membrane, indicating that succinate in the subretinal space serves as the GPR91 agonist. Excessive iron in the retina and RPE enhances GPR91 expression; however, VEGF expression does not always parallel GPR91 expression.

Indexed as

AnimalsBlotting, WesternCell LineFemaleFerric CompoundsGene Expression RegulationGene SilencingHemochromatosisHerpesviridae InfectionsHumansImmunohistochemistryIronMaleMiceMice, Inbred BALB CMice, Inbred C57BLferric ammonium citrateFerric CompoundsGPR91 protein, mouseIronQuaternary Ammonium CompoundsReceptors, G-Protein-CoupledRNA, MessengerSuccinic AcidVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouse

Identifiers

PMID21357408
PMCPMC3109050
OpenAlexW1987063004

What OpenQuestion holds

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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.