Evidence map›Paper›PMID 34184634›Full record

ArticleeLife2021

Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa.

Liyun Zhang, Conan Chen, Jie Fu, Brendan Lilley, Cynthia Berlinicke, Baranda Hansen, Ding Ding, Guohua Wang, Tao Wang, Daniel Shou and 20 more

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

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Ciliary Defects in Inherited Retinal Diseases.Advanced genetics (Hoboken, N.J.) · 2026
    Review
  5. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. An Overview towards Zebrafish Larvae as a Model for Ocular Diseases.International journal of molecular sciences · 2023
    Review
  15. Review
  16. Article
  17. Frontiers in pharmacology · 2022
    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

30 authors at 5 institutions in 4 countries.

Liyun ZhangDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Conan ChenDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Jie FuThe Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Brendan LilleyDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Cynthia BerlinickeDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Baranda HansenDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Ding DingDepartment of Biostatistics, Johns Hopkins University, Baltimore, United States.
Guohua WangDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Tao WangThe Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Daniel ShouThe Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Ying YeThe Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Timothy MulliganDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Kevin EmmerichDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Meera T SaxenaDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Kelsi R HallSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Abigail V SharrockDepartment of Biostatistics, Johns Hopkins University, Baltimore, United States.
Carlene BrandonDepartment of Ophthalmology, Medical University of South Carolina, Charleston, United States.
Hyejin ParkDepartment of Neurology, Johns Hopkins University, Baltimore, United States.
Tae-In KamDepartment of Neurology, Johns Hopkins University, Baltimore, United States.
Valina L DawsonDepartment of Neurology, Johns Hopkins University, Baltimore, United States.ORCID 0000-0002-2915-3970
Ted M DawsonDepartment of Neurology, Johns Hopkins University, Baltimore, United States.ORCID 0000-0002-6459-0893
Joong Sup ShimFaculty of Health Sciences, University of Macau, Taipa, Macau, China.
Justin HanesDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Hongkai JiDepartment of Biostatistics, Johns Hopkins University, Baltimore, United States.
Jun O LiuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, United States.ORCID 0000-0003-3842-9841
Jiang QianDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
David F AckerleySchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.ORCID 0000-0002-6188-9902
Baerbel RohrerDepartment of Ophthalmology, Medical University of South Carolina, Charleston, United States.
Donald J ZackDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.
Jeff S MummDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.ORCID 0000-0002-2575-287X
Johns Hopkins University · USMedical University of South Carolina · USVictoria University of Wellington · NZUniversity of Macau · MOXuzhou University of Technology · CN

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Genetic and Chemical Screens for Factors Regulating Retinal RegenerationR01EY022810 · NEI · JOHNS HOPKINS UNIVERSITY · PI MUMM, JEFFREY · 2013 to 2017
$2.1M
Alternative Pathway of Complement Activation in Age-Related Macular DegenerationR01EY019320 · NEI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ROHRER, BAERBEL · 2010 to 2014
$2.1M
Novel models of Alzheimer's Disease and Related Disorders enabling systematic investigation of the therapeutic potential of transplanted hiPSC-derived cells and endogenous adult neural stem cellsR01OD020376 · OD · JOHNS HOPKINS UNIVERSITY · PI MUMM, JEFFREY · 2016 to 2020
$2.1M
Complement Factor H Haplotypes and Smoking in Age-Related Macular DegenerationI01RX000444 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI Baerbel Rohrer · 2011 to 2026
–
BLR&D Research Career Scientist Award for Dr. Barbel RohrerIK6BX004858 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI Baerbel Rohrer · 2020 to 2026
–
RPE Cell Bystander Effects Contribute to AMD PathologyI01BX003050 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ROHRER, BAERBEL · 2016 to 2024
–
BLRD VA I01 BX003050NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY019320NEI NIH HHS R01 EY022810NIH HHS R01 OD020376RRD VA I01 RX000444
6 · The paper itself

Abstract

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP. We tested 2934 compounds, mostly human-approved drugs, across six concentrations, resulting in 113 compounds being identified as hits. Secondary tests of 42 high-priority hits confirmed eleven lead candidates. Leads were then evaluated in a series of mouse RP models in an effort to identify compounds effective across species and RP models, that is, potential pan-disease therapeutics. Nine of 11 leads exhibited neuroprotective effects in mouse primary photoreceptor cultures, and three promoted photoreceptor survival in mouse

Indexed as

AnimalsAnimals, Genetically ModifiedCells, CulturedCyclic Nucleotide Phosphodiesterases, Type 6Disease Models, AnimalDose-Response Relationship, DrugDrug Evaluation, PreclinicalGene Expression RegulationMiceMutationNeuroprotective AgentsPoly (ADP-Ribose) Polymerase-1Retinal Rod Photoreceptor CellsRetinitis PigmentosaZebrafishCyclic Nucleotide Phosphodiesterases, Type 6Neuroprotective AgentsPoly (ADP-Ribose) Polymerase-1developmental biologymouseneuroprotectantsneuroscienceretinitis pigmentosarod photoreceptorszebrafish

Identifiers

PMID34184634
PMCPMC8425951
OpenAlexW3173973658

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.