Evidence map›Paper›PMID 30721274›Full record

ArticleInvestigative ophthalmology & visual science2019

Stimulation of Retinal Pigment Epithelium With an α7 nAChR Agonist Leads to Müller Glia Dependent Neurogenesis in the Adult Mammalian Retina.

Mark K Webster, Betty J Barnett, Megan L Stanchfield, Joshua R Paris, Sarah E Webster, Cynthia A Cooley-Themm, Edward M Levine, Deborah C Otteson, Cindy L Linn

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Critical Examination of Müller Glia-DerivedFrontiers in cell and developmental biology · 2022
    Review
  10. Article
  11. Review
  12. BrdU Positive Cells Induced in a Genetic Mouse Model of Glaucoma.Journal of ophthalmology & visual sciences · 2021
    Article
  13. Review
  14. Involvement ofFrontiers in molecular biosciences · 2020
    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

9 authors at 4 institutions in 1 country.

Mark K WebsterWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Betty J BarnettWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Megan L StanchfieldWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Joshua R ParisWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Sarah E WebsterWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Cynthia A Cooley-ThemmWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Edward M LevineVanderbilt University Medical Center, Vanderbilt Eye Institute, Nashville, Tennessee, United States.
Deborah C OttesonUniversity of Houston College of Optometry, Department of Physiological Optics and Vision Science, Houston, Texas, United States.
Cindy L LinnWestern Michigan University, Department of Biological Sciences, Kalamazoo, Michigan, United States.
Michigan United · USWestern Michigan University · USUniversity of Houston · USVanderbilt University Medical Center · US

Funding

Novel Activators of Regeneration in Muller gliaU01EY027265 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LEVINE, EDWARD M, PATTON, JAMES G. · 2016 to 2018
$2.2M
Evidence of BrdU positive neurons in adult mammalian retina after treatment with an alpha7 nAChR agonistR15EY027970 · NEI · WESTERN MICHIGAN UNIVERSITY · PI LINN, CINDY L · 2018 to 2018
$453k
NEI NIH HHS R15 EY027970NEI NIH HHS U01 EY027265
6 · The paper itself

Abstract

Purpose: The adult mammalian retina is typically incapable of regeneration when damaged by disease or trauma. Restoration of function would require generation of new adult neurons, something that until recently, mammals were thought to be incapable of doing. However, previous studies from this laboratory have shown that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, PNU-282987, induces cell cycle reentry of Müller glia and generation of mature retinal neurons in adult rats, in the absence of detectible injury. This study analyzes how PNU-282987 treatment in RPE leads to robust BrdU incorporation in Müller glia in adult mice and leads to generation of Müller-derived retinal progenitors and neuronal differentiation. Methods: Retinal BrdU incorporation was examined after eye drop application of PNU-282987 in adult wild-type and transgenic mice that contain tamoxifen-inducible tdTomato Müller glia, or after intraocular injection of conditioned medium from PNU-282987-treated cultured RPE cells. Results: PNU-282987 induced robust incorporation of BrdU in all layers of the adult mouse retina. The α7 nAChR agonist was found to stimulate cell cycle reentry of Müller glia and their generation of new retinal progenitors indirectly, via the RPE, in an α7 nAChR-dependent fashion. Conclusions: The results from this study point to RPE as a contributor to Müller glial neurogenic responses. The manipulation of the RPE to stimulate retinal neurogenesis offers a new direction for developing novel and potentially transformative treatments to reverse the loss of neurons associated with neurodegenerative disease, traumatic injury, or aging.

Indexed as

alpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzamidesBridged Bicyclo CompoundsBromodeoxyuridineCell CycleCells, CulturedEpendymoglial CellsFemaleMaleMiceMice, TransgenicNeurogenesisNeurogliaNicotinic AgonistsPAX6 Transcription Factoralpha7 Nicotinic Acetylcholine ReceptorBenzamidesBridged Bicyclo CompoundsBromodeoxyuridineNicotinic AgonistsPax6 protein, mousePAX6 Transcription FactorPNU-282987

Identifiers

PMID30721274
PMCPMC6363405
OpenAlexW2914218494

What OpenQuestion 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 OpenQuestion graph.