Evidence map›Paper›PMID 30825184›Full record

ArticleBritish journal of pharmacology2019

Simvastatin protects photoreceptors from oxidative stress induced by all-trans-retinal, through the up-regulation of interphotoreceptor retinoid binding protein.

Ting Zhang, Mark Gillies, Ying Wang, Weiyong Shen, Bobak Bahrami, Shaoxue Zeng, Meidong Zhu, Wenjuan Yao, Fanfan Zhou, Michael Murray and 2 more

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

Article in British journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
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

12 authors at 2 institutions in 3 countries.

Ting ZhangSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Mark GilliesSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Ying WangSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Weiyong ShenSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Bobak BahramiSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Shaoxue ZengSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Meidong ZhuSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.
Wenjuan YaoSchool of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia.
Fanfan ZhouSchool of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia.
Michael MurrayDiscipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Ke WangKey Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
Ling ZhuSave Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0003-0776-1630
The University of Sydney · AUMinistry Of Health · FJ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeSimvastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor with multiple targets and effects. It protects neurons in the brain, but its protective effects on photoreceptors are unclear. In this study, we evaluated the neuroprotective effect of simvastatin on photoreceptors exposed to stress induced by all-trans-retinal (atRAL). EXPERIMENTAL APPROACH: AlamarBlue and LDH assays were used to evaluate the viability and metabolic activity of Y79 cells (a retinoblastoma cell line) exposed to atRAL-induced stress with or without simvastatin pretreatment. Changes in cellular ROS were evaluated using flow cytometry and mitochondrial stress markers JC-1 and HSP60. Changes in levels of two photoreceptor-specific markers, cone-rod homeobox protein (CRX) and interphotoreceptor retinoid binding protein (IRBP), were evaluated with western blot. The results were validated in ex vivo human retinal explants and a mouse model of photoreceptor degeneration. KEY

resultsSimvastatin improved mitochondrial function, alleviated oxidative stress and up-regulated the photoreceptor-specific markers IRBP and its upstream regulator CRX in Y79 cells and ex vivo human retinal explants under atRAL-induced stress. Simvastatin attenuated photoreceptor degeneration in association with up-regulation of IRBP and CRX expression after knockdown of IRBP in a murine model. CONCLUSION AND IMPLICATIONS: Our findings suggest that simvastatin has a novel role in protecting photoreceptors from atRAL-induced stress. Simvastatin treatment resulted in up-regulation of IRBP and its upstream transcription factor CRX in Y79 cells, ex vivo human retinal explants, and murine retinas in vivo. Further studies of simvastatin to treat photoreceptor degeneration are warranted.

Indexed as

AnimalsAntineoplastic Agents, HormonalCells, CulturedCell SurvivalDose-Response Relationship, DrugHumansInjections, IntraperitonealMiceMice, TransgenicMolecular StructureOxidative StressProtective AgentsRetinal Cone Photoreceptor CellsRetinol-Binding ProteinsSimvastatinStructure-Activity RelationshipAntineoplastic Agents, HormonalProtective AgentsRetinol-Binding ProteinsSimvastatinTamoxifenTretinoin

Identifiers

PMID30825184
PMCPMC6534793
OpenAlexW2920199763

What Socratic 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 Socratic graph.