Evidence map›Paper›PMID 30695061›Full record

ArticlePLoS genetics2019

Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation.

Nicholas J Hanovice, Lyndsay L Leach, Kayleigh Slater, Ana E Gabriel, Dwight Romanovicz, Enhua Shao, Ross Collery, Edward A Burton, Kira L Lathrop, Brian A Link and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

40 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
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  9. Different Therapeutic Approaches for Dry and Wet AMD.International journal of molecular sciences · 2024
    Review
  10. Article
  11. Article
  12. Modeling complex age-related eye disease.Progress in retinal and eye research · 2024
    Review
  13. Article
  14. Article
  15. Molecular and cellular imaging of the eye.Biomedical optics express · 2024
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

11 authors at 3 institutions in 2 countries.

Nicholas J HanoviceDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0003-0827-6071
Lyndsay L LeachDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-5138-1371
Kayleigh SlaterDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0001-5566-8399
Ana E GabrielDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0001-7282-5544
Dwight RomanoviczCenter for Biomedical Research Support, The University of Texas at Austin, Austin, Texas, United States of America.
Enhua ShaoPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Ross ColleryDepartment of Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.ORCID 0000-0002-1550-299X
Edward A BurtonPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-8072-4636
Kira L LathropDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Brian A LinkDepartment of Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
Jeffrey M GrossDepartment of Ophthalmology, Louis J Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-9422-6312
University of Pittsburgh · USMedical College of Wisconsin · USThe University of Texas at Austin · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
NEI NIH HHS P30 EY008098
6 · The paper itself

Abstract

The retinal pigment epithelium (RPE) is a specialized monolayer of pigmented cells within the eye that is critical for maintaining visual system function. Diseases affecting the RPE have dire consequences for vision, and the most prevalent of these is atrophic (dry) age-related macular degeneration (AMD), which is thought to result from RPE dysfunction and degeneration. An intriguing possibility for treating RPE degenerative diseases like atrophic AMD is the stimulation of endogenous RPE regeneration; however, very little is known about the mechanisms driving successful RPE regeneration in vivo. Here, we developed a zebrafish transgenic model (rpe65a:nfsB-eGFP) that enabled ablation of large swathes of mature RPE. RPE ablation resulted in rapid RPE degeneration, as well as degeneration of Bruch's membrane and underlying photoreceptors. Using this model, we demonstrate for the first time that zebrafish are capable of regenerating a functional RPE monolayer after RPE ablation. Regenerated RPE cells first appear at the periphery of the RPE, and regeneration proceeds in a peripheral-to-central fashion. RPE ablation elicits a robust proliferative response in the remaining RPE. Subsequently, proliferative cells move into the injury site and differentiate into RPE. BrdU incorporation assays demonstrate that the regenerated RPE is likely derived from remaining peripheral RPE cells. Pharmacological disruption using IWR-1, a Wnt signaling antagonist, significantly reduces cell proliferation in the RPE and impairs overall RPE recovery. These data demonstrate that the zebrafish RPE possesses a robust capacity for regeneration and highlight a potential mechanism through which endogenous RPE regenerate in vivo.

Indexed as

AnimalsAnimals, Genetically ModifiedApoptosisBruch MembraneCell Differentiationcis-trans-IsomerasesDisease Models, AnimalGreen Fluorescent ProteinsHumansImidesLarvaMacular DegenerationPhotoreceptor CellsQuinolinesRegenerationRetinacis-trans-IsomerasesGreen Fluorescent ProteinsImidesIWR-1 compoundQuinolinesRetinoid Isomerohydrolase

Identifiers

PMID30695061
PMCPMC6368336
OpenAlexW2950478324

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.