Evidence map›Paper›PMID 36206764›Full record

ArticleStem cell reports2022

Human retinal organoids harboring IMPG2 mutations exhibit a photoreceptor outer segment phenotype that models advanced retinitis pigmentosa.

Steven J Mayerl, Simona Bajgai, Allison L Ludwig, Lindsey D Jager, Brittany N Williams, Cole Bacig, Christopher Stoddard, Divya Sinha, Benjamin D Philpot, David M Gamm

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

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  10. A highly reproducible and efficient method for retinal organoid differentiation from human pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

10 authors at 4 institutions in 1 country.

Steven J MayerlCellular and Molecular Pathology University of Wisconsin-Madison, Madison, WI, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Simona BajgaiWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Allison L LudwigMcPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA; Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Lindsey D JagerWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Brittany N WilliamsDepartment of Cell Biology & Physiology, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA.
Cole BacigWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Christopher StoddardDepartment of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, USA.
Divya SinhaMcPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Benjamin D PhilpotDepartment of Cell Biology & Physiology, University of North Carolina, Chapel Hill, NC, USA; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA; Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA.
David M GammCellular and Molecular Pathology University of Wisconsin-Madison, Madison, WI, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: dgamm@wisc.edu.
University of Wisconsin–Madison · USUniversity of North Carolina at Chapel Hill · USSmith-Kettlewell Eye Research Institute · USUniversity of Connecticut · US

Funding

Postdoctoral Research in Neurodevelopmental DisordersT32HD040127 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BENJAMIN D PHILPOT, Mark D Shen · 2001 to 2026
$8.5M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI KUNKEL, LOUIS M · 2016 to 2020
$5.2M
Toward enhancing organization and defining synaptic connectivity of transplanted human pluripotent stem cell-derived photoreceptor graftsF30EY031230 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI LUDWIG, ALLISON LYN · 2020 to 2023
$163k
NEI NIH HHS F30 EY031230NICHD NIH HHS T32 HD040127NICHD NIH HHS U54 HD090255
6 · The paper itself

Abstract

Interphotoreceptor matrix proteoglycan 2 (IMPG2) mutations cause a severe form of early-onset retinitis pigmentosa (RP) with macular involvement. IMPG2 is expressed by photoreceptors and incorporated into the matrix that surrounds the inner and outer segments (OS) of rods and cones, but the mechanism of IMPG2-RP remains unclear. Loss of Impg2 function in mice produces a mild, late-onset photoreceptor phenotype without the characteristic OS loss that occurs in human patients. We generated retinal organoids (ROs) from patient-derived induced pluripotent stem (iPS) cells and gene-edited embryonic stem cells to model human IMPG2-RP in vitro. All ROs harboring IMPG2 mutations lacked an OS layer, in contrast to isogenic controls. Subsequent protein analyses revealed that this phenotype arises due to a loss of IMPG2 expression or its inability to undergo normal post-translational modifications. We hypothesized that loss of IMPG2 function destabilizes the interphotoreceptor matrix and renders the OS vulnerable to physical stressors, which is accentuated in the tissue culture environment. In support of this mechanism, transplantation of IMPG2 mutant ROs into the protected subretinal space of immunocompromised rodents restored OS production. Beyond providing a robust platform to study IMPG2-RP, this human RO model system may serve a broader role in honing strategies to treat advanced photoreceptor-based diseases.

Indexed as

OrganoidsRetinitis PigmentosaAnimalsEye ProteinsHumansMiceMutationPhenotypeProteoglycansReactive Oxygen SpeciesRetinaRetinal Cone Photoreceptor CellsEye ProteinsIMPG2 protein, humanImpg2 protein, mouseProteoglycansReactive Oxygen Speciesdisease modelingIMPG2photoreceptorsretinal organoidretinitis pigmentosastem cells

Identifiers

PMID36206764
PMCPMC9669399
OpenAlexW4303056912

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.