Evidence map›Paper›PMID 24462739›Full record

ArticleBiochimica et biophysica acta2014

Regulation of the cholesterol efflux transporters ABCA1 and ABCG1 in retina in hemochromatosis and by the endogenous siderophore 2,5-dihydroxybenzoic acid.

Sudha Ananth, Jaya P Gnana-Prakasam, Yangzom D Bhutia, Rajalakshmi Veeranan-Karmegam, Pamela M Martin, Sylvia B Smith, Vadivel Ganapathy

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
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  4. Dietary effects on the retina of hamsters.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

7 authors at 1 institution in 1 country.

Sudha AnanthDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
Jaya P Gnana-PrakasamDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
Yangzom D BhutiaDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
Rajalakshmi Veeranan-KarmegamDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
Pamela M MartinDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
Sylvia B SmithDepartment of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
Vadivel GanapathyDepartment of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: vganapat@gru.edu.
Augusta University · US

Funding

Role of homocysteine in retinal diseaseR01EY012830 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI SMITH, SYLVIA B. · 2000 to 2016
$4.4M
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
Molecular basis of inflammation in retina, and novel strategies for limiting itR01EY022704 · NEI · AUGUSTA UNIVERSITY · PI MARTIN, PAMELA M · 2014 to 2018
$2.2M
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 EY019672NEI NIH HHS R01 EY022704
6 · The paper itself

Abstract

Hypercholesterolemia and polymorphisms in the cholesterol exporter ABCA1 are linked to age-related macular degeneration (AMD). Excessive iron in retina also has a link to AMD pathogenesis. Whether these findings mean a biological/molecular connection between iron and cholesterol is not known. Here we examined the relationship between retinal iron and cholesterol using a mouse model (Hfe(-/-)) of hemochromatosis, a genetic disorder of iron overload. We compared the expression of the cholesterol efflux transporters ABCA1 and ABCG1 and cholesterol content in wild type and Hfe(-/-) mouse retinas. We also investigated the expression of Bdh2, the rate-limiting enzyme in the synthesis of the endogenous siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA) in wild type and Hfe(-/-) mouse retinas, and the influence of this siderophore on ABCA1/ABCG1 expression in retinal pigment epithelium. We found that ABCA1 and ABCG1 were expressed in all retinal cell types, and that their expression was decreased in Hfe(-/-) retina. This was accompanied with an increase in retinal cholesterol content. Bdh2 was also expressed in all retinal cell types, and its expression was decreased in hemochromatosis. In ARPE-19 cells, 2,5-DHBA increased ABCA1/ABCG1 expression and decreased cholesterol content. This was not due to depletion of free iron because 2,5-DHBA (a siderophore) and deferiprone (an iron chelator) had opposite effects on transferrin receptor expression and ferritin levels. We conclude that iron is a regulator of cholesterol homeostasis in retina and that removal of cholesterol from retinal cells is impaired in hemochromatosis. Since excessive cholesterol is pro-inflammatory, hemochromatosis might promote retinal inflammation via cholesterol in AMD.

Indexed as

AnimalsATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1CholesterolDNA MethylationGentisatesHemochromatosisHemochromatosis ProteinHistocompatibility Antigens Class ILipoproteinsMembrane ProteinsMiceMice, Inbred BALB CRetinaSiderophores2,5-dihydroxybenzoic acidAbca1 protein, mouseABCG1 protein, mouseATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 1CholesterolGentisatesHemochromatosis ProteinHfe protein, mouseHistocompatibility Antigens Class ILipoproteinsMembrane ProteinsSiderophoresCholesterol transportHemochromatosisMammalian siderophoreRetinal pigment epithelial cellsβ-Hydroxybutyrate dehydrogenase-2

Identifiers

PMID24462739
PMCPMC4289134
OpenAlexW2100804445

What OpenQuestion holds

Textmetadata
LicenceTDM
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.