Evidence map›Paper›PMID 22467575›Full record

ArticleInvestigative ophthalmology & visual science2012

Compound 49b prevents diabetes-induced apoptosis through increased IGFBP-3 levels.

Qiuhua Zhang, Kimberly Guy, Jayaprakash Pagadala, Youde Jiang, Robert J Walker, Luhong Liu, Carl Soderland, Timothy S Kern, Robert Ferry, Hui He and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

54 citing papers in PubMed, 59 citations in OpenAlex.

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  18. PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018
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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

13 authors at 3 institutions in 1 country.

Qiuhua ZhangDepartment of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Kimberly Guy
Jayaprakash Pagadala
Youde Jiang
Robert J Walker
Luhong Liu
Carl Soderland
Timothy S Kern
Robert Ferry
Hui He
C Ryan Yates
Duane D Miller
Jena J Steinle
Ophthalmology Associates (United States) · USPediatrics and Genetics · USUniversity of Tennessee Health Science Center · US

Funding

STUDY OF DIABETIC RETINOPATHYR01EY000300 · NEI · UNIVERSITY OF WISCONSIN MADISON · PI KERN, TIMOTHY S · 1985 to 2013
$4.7M
CORE--MOLECULAR BIOLOGYP30EY013080 · NEI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JOHNSON, DIANNA AMMONS · 2000 to 2010
$3.7M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Compound 49b Prevents Retinal Endothelial Cell Death Through IGFBP-3 LevelsR01EY022045 · NEI · WAYNE STATE UNIVERSITY · PI STEINLE, JENA J · 2012 to 2016
$1.8M
Study of diabetic retinopathyR56EY000300 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI KERN, TIMOTHY S · 2009 to 2009
$353k
Beta-Adrenergic Receptor Modulation of Insulin SignalingF31EY019240 · NEI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WALKER, ROBERT · 2008 to 2012
$101k
NEI NIH HHS 3P30 EY013080NEI NIH HHS EY00300NEI NIH HHS F31 EY019240NEI NIH HHS F31EY019240-02NEI NIH HHS P30 EY013080NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY000300NEI NIH HHS R01 EY022045NEI NIH HHS R56 EY000300
6 · The paper itself

Abstract

purposeTo determine whether Compound 49b, a novel PKA-activating drug, can prevent diabetic-like changes in the rat retina through increased insulin-like growth factor binding protein-3 (IGFBP-3) levels.

methodsFor the cell culture studies, we used both human retinal endothelial cells (REC) and retinal Müller cells in either 5 mM (normal) or 25 mM (high) glucose. Cells were treated with 50 nM Compound 49b alone of following treatment with protein kinase A (PKA) siRNA or IGFBP-3 siRNA. Western blotting and ELISA analyses were done to verify PKA and IGFBP-3 knockdown, as well as to measure apoptotic markers. For animal studies, we used streptozotocin-treated rats after 2 and 8 months of diabetes. Some rats were treated topically with 1 mM Compound 49b. Analyses were done for retinal thickness, cell numbers in the ganglion cell layer, pericyte ghosts, and numbers of degenerate capillaries, as well as electroretinogram and heart morphology.

resultsCompound 49b requires active PKA and IGFBP-3 to prevent apoptosis of REC. Compound 49b significantly reduced the numbers of degenerate capillaries and pericyte ghosts, while preventing the decreased retinal thickness and loss of cells in the ganglion cell layer. Compound 49b maintained a normal electroretinogram, with no changes in blood pressure, intraocular pressure, or heart morphological changes.

conclusionsTopical Compound 49b is able to prevent diabetic-like changes in the rat retina, without producing systemic changes. Compound 49b is able to prevent REC apoptosis through increasing IGFBP-3 levels, which are reduced in response to hyperglycemia.

Indexed as

Adrenergic beta-AgonistsAnimalsApoptosisCells, CulturedCyclic AMP-Dependent Protein KinasesDiabetes Mellitus, ExperimentalDiabetic RetinopathyDose-Response Relationship, DrugElectroretinographyEndothelial CellsEnzyme-Linked Immunosorbent AssayHeart VentriclesInsulin-Like Growth Factor Binding Protein 3MaleOphthalmic SolutionsRatsAdrenergic beta-AgonistsCyclic AMP-Dependent Protein KinasesInsulin-Like Growth Factor Binding Protein 3Ophthalmic SolutionsRNA, Small Interfering

Identifiers

PMID22467575
PMCPMC3378083
OpenAlexW2009107512

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.