Evidence map›Paper›PMID 42497345›Full record

ArticleDisease models & mechanisms2026

Cell death analysis of inducible, titratable neurodegenerative disease models in zebrafish and human stem cell-derived retinal organoids.

Anneliese Ceisel, Gianna Graziano, Kevin Emmerich, Xiangqian Shi, Tae-In Kam, Miguel Flores-Bellver, M Natalia Vergara, Silvia Aparicio-Domingo, Boris M Brenerman, Anne Vielle and 26 more

Abstract read
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In one paragraph

Article in Disease models & mechanisms, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

36 authors.

Anneliese CeiselWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Gianna GrazianoWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Kevin EmmerichWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Xiangqian ShiWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Tae-In KamNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Miguel Flores-BellverCellSight Ocular Stem Cell and Regeneration Research Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado Anschutz, Aurora, CO 80045, USA.
M Natalia VergaraCellSight Ocular Stem Cell and Regeneration Research Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado Anschutz, Aurora, CO 80045, USA.
Silvia Aparicio-DomingoCellSight Ocular Stem Cell and Regeneration Research Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado Anschutz, Aurora, CO 80045, USA.
Boris M BrenermanSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Anne VielleCellSight Ocular Stem Cell and Regeneration Research Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado Anschutz, Aurora, CO 80045, USA.
Elsie M WilliamsSchool of Biological Sciences, Victoria University of Wellington. Wellington 6140, New Zealand.
Abigail V SharrockSchool of Biological Sciences, Victoria University of Wellington. Wellington 6140, New Zealand.
Uche OnuchuwkuWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Georgina S MartinezWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Lydia G SandersWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Uzoamaka NwagboDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Beichen WangDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Huanhuan XiaoWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Grant KroeschellWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Yiqi GaoWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Daniel J ChoeWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Caroline E ClouatreWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Diego Alfaro CarcobaWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Barak ReibmanWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Catalina RodriguezWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Kevin YangWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Shreya BanerjeeWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Frazer MatthewsWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
James H ThiererWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Genevieve Stein-O'BrienSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
David F AckerleySchool of Biological Sciences, Victoria University of Wellington. Wellington 6140, New Zealand.
M Valeria Canto-SolerTranslational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Liyun ZhangWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0003-3306-0459
Jeff S MummWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.ORCID 0000-0002-2575-287X

Funding

CORE--TRANSMISSION &IMAGING EMP30EY001765 · JOHNS HOPKINS UNIVERSITY · 1985 to 2005
$3.7M
Resolving Spatiotemporal Determinants of Cell Specification in Corticogenesis with Latent Space MethodsR00NS122085 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$224k
BrightFocus Foundation M2024008NCellSight Development FundDoni Solich Family Chair in Ocular Stem Cell ResearchDr. Ralph and Marian Falk Medical Research TrustFoundation Fighting BlindnessJohns Hopkins UniversityMarsden Fund VUW1902Marsden Fund VUW2402Maryland Department of CommerceNEI NIH HHS F31:EY032790NEI NIH HHS F31:EY037171NEI NIH HHS P30 EY001765NEI NIH HHS P30:EY1765NEI NIH HHS R01:EY032533NEI NIH HHS R01:EY033009NEI NIH HHS R01:OD020376NEI NIH HHS T32:EY7143-22NIH HHS R01 OD020376NIH HHS S10 OD026909NINDS NIH HHS R00 NS122085Research to Prevent BlindnessSchool of Medicine, Johns Hopkins University
6 · The paper itself

Abstract

Inducible disease models enable large-scale screening by providing control over pathology onset, such as cell death in neurodegenerative disease. The nitroreductase (NTR)/prodrug system of cell ablation has facilitated investigations of cell function and regeneration but has not been widely adopted as a disease modeling platform, perhaps owing to assumptions that the cell death mechanism(s) elicited is artificial in nature. Prior reports suggested that NTR/prodrug-mediated death occurred through apoptosis, necroptosis and/or parthanatos, which have all been implicated in neurodegenerative disease. To clarify this issue, we investigated the cell death pathway(s) elicited by the prodrug metronidazole (MTZ) with improved nitroreductase enzyme variants. We assessed the cell death pathway(s) elicited by NTR 2.0-expressing zebrafish retinal neurons using a transcriptomic analysis, chemical inhibitors and gene-targeting assays. NTR-H, a novel NTR variant, was tested - and found to be effective - in human stem cell-derived retinal organoids. Parthanatos was implicated across all conditions tested, while evidence of apoptosis was variable. As parthanatos is associated with neurodegeneration, our results support the use of the NTR/MTZ system to create inducible neurodegenerative models targeted to specific disease-relevant neuronal cell types.

Indexed as

Neurodegenerative DiseasesOrganoidsRetinaStem CellsZebrafishAnimalsApoptosisCell DeathDisease Models, AnimalHumansMetronidazoleNitroreductasesMetronidazoleNitroreductasesCell deathInducible disease modelNeurodegenerationNitroreductaseParthanatosRetinal organoids

Identifiers

PMID42497345

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.