Evidence map›Paper›PMID 25813825›Full record

ArticleBrain research2015

Celastrol supports survival of retinal ganglion cells injured by optic nerve crush.

Haksu Kyung, Jacky M K Kwong, Vlad Bekerman, Lei Gu, Daniel Yadegari, Joseph Caprioli, Natik Piri

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Indirect traumatic optic neuropathy.Military Medical Research · 2016
    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

7 authors.

Haksu KyungJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA; National Medical Center, Seoul, Republic of Korea.
Jacky M K KwongJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
Vlad BekermanJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
Lei GuJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
Daniel YadegariJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
Joseph CaprioliJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA.
Natik PiriJules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: piri@jsei.ucla.edu.

Funding

Vision Research Core at UCLAP30EY000331 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gregory Darin Field, DAVID S WILLIAMS · 1985 to 2026
$16.8M
The Neuroprotective Effect of HSP72 Induction in Experimental GlaucomaR01EY018644 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIRI, NATIK · 2009 to 2013
$1.3M
NEI NIH HHS EY018644NEI NIH HHS P30 EY000331NEI NIH HHS R01 EY018644
6 · The paper itself

Abstract

The present study evaluates the effect of celastrol on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii (Celastraceae), has been identified as a potential neuroprotective candidate in a comprehensive drug screen against various neurodegenerative diseases. Two weeks after ONC, the average density of remaining RGCs in retinas of animals treated with daily intraperitoneal (i.p.) injections of celastrol (1mg/kg) was approximately 1332 cells/mm(2), or 40.8% of the Celastrol/Control group. In retinas of the Vehicle/ONC group about 381 RGCs/mm(2) were counted, which is 9.6% of the total number of RGCs in the DMSO/Control group. This corresponds to approximately a 250% increase in RGC survival mediated by celastrol treatment compared to Vehicle/ONC group. Furthermore, the average RGC number in retinas of ONC animals treated with a single intravitreal injection of 1mg/kg or 5mg/kg of celastrol was increased by approximately 80% (760 RGCs/mm(2)) and 78% (753 RGCs/mm(2)), respectively, compared to Vehicle/ONC controls (422 cells/mm(2)). Injection of 0.2mg/kg of celastrol had no significant effect on cell survival, with the average number of RGCs being 514 cells/mm(2) in celastrol-treated animals versus 422 cells/mm(2) in controls. The expression levels of Hsp70, Hsf1, Hsf2, HO-1 and TNF-alpha in the retina were analyzed to evaluate the roles of these proteins in the celastrol-mediated protection of injured RGCs. No statistically significant change in HO-1, Hsf1 and Hsp70 levels was seen in animals with ONC. An approximately 2 fold increase in Hsf2 level was observed in celastrol-treated animals with or without injury. Hsf2 level was also increased 1.8 fold in DMSO-treated animals with ONC injury compared to DMSO-treated animals with no injury suggesting that Hsf2 induction has an injury-induced component. Expression of TNF-alpha in retinas of celastrol-treated uninjured and ONC animals was reduced by approximately 2 and 1.5 fold compared to vehicle treated animals, respectively. The observed results suggest that mechanisms underlying celastrol׳s RGC protective effect are associated with inhibition of TNF-alpha-mediated cell death.

Indexed as

AnimalsBody WeightCell CountCell SurvivalDisease Models, AnimalDNA-Binding ProteinsDown-RegulationHeat-Shock ProteinsHeat Shock Transcription FactorsHeme Oxygenase (Decyclizing)HSP70 Heat-Shock ProteinsNerve CrushNeuroprotective AgentsOptic NerveOptic Nerve InjuriesPentacyclic TriterpenescelastrolDNA-Binding ProteinsHeat-Shock ProteinsHeat Shock Transcription FactorsHeme Oxygenase (Decyclizing)Hmox1 protein, ratHsf1 protein, ratHsf2 protein, ratHSP70 Heat-Shock ProteinsNeuroprotective AgentsPentacyclic TriterpenesTranscription FactorsTriterpenesTumor Necrosis Factor-alphaCelastrolGanglion cellsNeuroprotectionOptic nerveRetina

Identifiers

PMID25813825
PMCPMC4417422

What OpenQuestion holds

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Read underepoch 390

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.