Evidence map›Paper›PMID 24408986›Full record

ArticleInvestigative ophthalmology & visual science2014

Control of photoreceptor autophagy after retinal detachment: the switch from survival to death.

Nicholas D Chinskey, Qiong-Duon Zheng, David N Zacks

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

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  20. Regulatory role of calpain in neuronal death.Neural regeneration research · 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

3 authors at 2 institutions in 1 country.

Nicholas D ChinskeyDepartment of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan.
Qiong-Duon Zheng
David N Zacks
University of Michigan–Ann Arbor · USAnn Arbor Center for Independent Living · US

Funding

VIVARIUM MODULEP30EY007003 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti · 1987 to 2026
$17.6M
Molecular Regulation of Photoreceptor Cell DeathR01EY020823 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABCOUWER, STEVEN F, ZACKS, DAVID N · 2010 to 2023
$5.0M
E75 IN THE DEVELOPING DROSOPHILA EYEF31EY007003 · NEI · YALE UNIVERSITY · PI SHILTON, ALYCIA N · 1999 to 2001
$14k
NEI NIH HHS EY007003NEI NIH HHS EY020823NEI NIH HHS F31 EY007003NEI NIH HHS P30 EY007003NEI NIH HHS R01 EY020823
6 · The paper itself

Abstract

purposeTo examine whether calpain inhibition following retinal detachment would prolong autophagy and result in reduced photoreceptor apoptosis.

methodsRetinal detachments were created in Brown-Norway rats by subretinal injection of 1% hyaluronic acid and simulated in vitro by Fas-receptor activation of 661W cells, a cone cell line. Protein levels of LC3 and autophagy-related gene 5 (Atg5), both of which are involved in the creation of the autophagosome, were assayed by Western blot. Calpain 1, the protease responsible for Atg5 cleavage and transitioning photoreceptors from autophagy to apoptosis, activity was monitored by α-spectrin cleavage. Various calpain inhibitors were added either to the subretinal space or cell culture media. Apoptosis was assessed in vitro by caspase-8 activity assays and in vivo via TUNEL assays. Cell counts were assessed in vivo at 2 months following detachment.

resultsFollowing retinal detachment or Fas-receptor activation of 661W cells, there was an increase in Atg5 and LC3-II that peaked at 3 days and decreased by 7-days postdetachment. Calpain 1 activity level peaked at 7 days and was associated with decreased autophagy. Calpain inhibition led to increased autophagy, a decrease in caspase-8 activation, reduced TUNEL-positive photoreceptors, and increased photoreceptor cell survival.

conclusionsOur data suggest that calpain activation, which peaks at 7-days postdetachment, is a key step in triggering photoreceptors to shift from cell survival to death. Prolonging autophagy through calpain inhibition leads to significantly reduced photoreceptor apoptosis and increased cell survival.

Indexed as

ApoptosisAnimalsAutophagyAutophagy-Related Protein 5Blotting, WesternCalpainCaspase 8Cell LineCell SurvivalDisease Models, AnimalEnzyme Inhibitorsfas ReceptorIn Situ Nick-End LabelingMacrolidesMaleMicrotubule-Associated ProteinsAnxa3 protein, ratAtg5 protein, ratAutophagy-Related Protein 5bafilomycin ACalpainCasp8 protein, ratCaspase 8Enzyme Inhibitorsfas ReceptorMacrolidesMicrotubule-Associated ProteinsProteinsapoptosisautophagyretinal detachment

Identifiers

PMID24408986
PMCPMC3915768
OpenAlexW1998650503

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.