Evidence map›Paper›PMID 33657370›Full record

ArticleCell reports2021

Optic nerve regeneration screen identifies multiple genes restricting adult neural repair.

Jane A Lindborg, Nicholas M Tran, Devon M Chenette, Kristin DeLuca, Yram Foli, Ramakrishnan Kannan, Yuichi Sekine, Xingxing Wang, Marius Wollan, In-Jung Kim and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

36 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
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  7. Article
  8. Article
  9. Article
  10. Cutting-edge technologies in neural regeneration.Cell regeneration (London, England) · 2025
    Review
  11. The neuroimmune interface in retinal regeneration.Progress in retinal and eye research · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
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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

12 authors at 2 institutions in 1 country.

Jane A LindborgCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Nicholas M TranCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Devon M ChenetteCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Kristin DeLucaCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Yram FoliCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Ramakrishnan KannanCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Yuichi SekineCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Xingxing WangCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
Marius WollanCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
In-Jung KimDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06536, USA.
Joshua R SanesCenter for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Stephen M StrittmatterCellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: stephen.strittmatter@yale.edu.
Yale University · USHarvard University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Genome-Wide Discovery and Translational Research for Neural RepairR35NS097283 · NINDS · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2017 to 2024
$8.1M
Yale Core Grant for Vision ResearchP30EY026878 · NEI · YALE UNIVERSITY · PI Jonathan B Demb · 2016 to 2026
$7.1M
Molecular Genetics of Visual Circuit Assembly in the Developing Superior ColliculusR01EY031751 · NEI · YALE UNIVERSITY · PI KIM, IN-JUNG · 2020 to 2024
$2.1M
Evaluation of Novel Targets for Retinal Ganglion Cell Axon RegenerationU01EY027256 · NEI · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2016 to 2018
$2.0M
Visual Science Training GrantT32EY022312 · NEI · YALE UNIVERSITY · PI ZHOU, Z JIMMY · 2012 to 2021
$1.3M
Determinants of type-dependent retinal ganglion cell resilience: potential targets for neuroprotection and axon regenerationR00EY029360 · NEI · BAYLOR COLLEGE OF MEDICINE · PI TRAN, NICHOLAS MINH ABELL · 2021 to 2023
$740k
Molecular Mechanisms of Visual Circuit Formation between Superior Colliculus and ThalamusR21EY029820 · NEI · YALE UNIVERSITY · PI KIM, IN-JUNG · 2019 to 2020
$461k
Determinants of type-dependent retinal ganglion cell resilience: potential targets for neuroprotection and axon regenerationK99EY029360 · NEI · HARVARD UNIVERSITY · PI TRAN, NICHOLAS MINH ABELL · 2018 to 2020
$268k
Subtype-specific Retinal Ganglion Cell Degeneration and Regeneration following Optic Nerve CrushF32EY028448 · NEI · HARVARD UNIVERSITY · PI TRAN, NICHOLAS MINH ABELL · 2017 to 2017
$59k
NCATS NIH HHS UL1 TR001863NEI NIH HHS F32 EY028448NEI NIH HHS K99 EY029360NEI NIH HHS P30 EY026878NEI NIH HHS R00 EY029360NEI NIH HHS R01 EY031751NEI NIH HHS R21 EY029820NEI NIH HHS T32 EY022312NEI NIH HHS U01 EY027256NINDS NIH HHS R35 NS097283
6 · The paper itself

Abstract

Adult mammalian central nervous system (CNS) trauma interrupts neural networks and, because axonal regeneration is minimal, neurological deficits persist. Repair via axonal growth is limited by extracellular inhibitors and cell-autonomous factors. Based on results from a screen in vitro, we evaluate nearly 400 genes through a large-scale in vivo regeneration screen. Suppression of 40 genes using viral-driven short hairpin RNAs (shRNAs) promotes retinal ganglion cell (RGC) axon regeneration after optic nerve crush (ONC), and most are validated by separate CRISPR-Cas9 editing experiments. Expression of these axon-regeneration-suppressing genes is not significantly altered by axotomy. Among regeneration-limiting genes, loss of the interleukin 22 (IL-22) cytokine allows an early, yet transient, inflammatory response in the retina after injury. Reduced IL-22 drives concurrent activation of signal transducer and activator of transcription 3 (Stat3) and dual leucine zipper kinase (DLK) pathways and upregulation of multiple neuron-intrinsic regeneration-associated genes (RAGs). Including IL-22, our screen identifies dozens of genes that limit CNS regeneration. Suppression of these genes in the context of axonal damage could support improved neural repair.

Indexed as

AnimalsAxonsCRISPR-Cas SystemsDependovirusFemaleGene EditingGene Expression RegulationGenetic Association StudiesHEK293 CellsHumansInterleukin-22InterleukinsMaleMAP Kinase Kinase KinasesMiceMice, Inbred C57BLInterleukin-22InterleukinsMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12Stat3 protein, mouseSTAT3 Transcription FactorAAVaxon regenerationCRISPRgene editingIL-22inflammationoptic nerveretinashRNA

Identifiers

PMID33657370
PMCPMC8009559
OpenAlexW3134588537

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.