Evidence map›Paper›PMID 38834544›Full record

ArticleNature communications2024

Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders.

Christian T Rutan Woods, Mustafa S Makia, Tylor R Lewis, Ryan Crane, Stephanie Zeibak, Paul Yu, Mashal Kakakhel, Carson M Castillo, Vadim Y Arshavsky, Muna I Naash and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Genes · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Christian T Rutan WoodsDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.ORCID http://orcid.org/0009-0003-9061-6545
Mustafa S MakiaDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
Tylor R LewisDepartment of Ophthalmology, Duke University Medical Center, Durham, NC, 27710, USA.ORCID http://orcid.org/0000-0001-6832-7972
Ryan CraneDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.
Stephanie ZeibakDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.ORCID http://orcid.org/0009-0002-2003-5633
Paul YuDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.ORCID http://orcid.org/0009-0003-2745-6980
Mashal KakakhelDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA.ORCID http://orcid.org/0000-0001-9516-8161
Carson M CastilloDepartment of Ophthalmology, Duke University Medical Center, Durham, NC, 27710, USA.
Vadim Y ArshavskyDepartment of Ophthalmology, Duke University Medical Center, Durham, NC, 27710, USA.ORCID http://orcid.org/0000-0001-8394-3650
Muna I NaashDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA. mnaash@central.uh.edu.ORCID http://orcid.org/0000-0002-6534-5144
Muayyad R Al-UbaidiDepartment of Biomedical Engineering, University of Houston, Houston, TX, 77204, USA. malubaid@central.uh.edu.ORCID http://orcid.org/0000-0002-4914-350X

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Goldis Malek · 1985 to 2026
$19.3M
Supplement for: Mechanism of Photoreceptor Cell Degeneration in Animal Models of Retinal DiseasesR01EY010609 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI MUAYYAD R AL-UBAIDI, Muna I. Naash · 1995 to 2026
$11.0M
Mechanisms of photoreceptor disc maturationR01EY030451 · NEI · DUKE UNIVERSITY · PI ARSHAVSKY, VADIM Y · 2020 to 2024
$2.4M
Non-viral gene delivery platforms for the treatment of Usher Syndrome Type 2A.R01EY034671 · NEI · UNIVERSITY OF HOUSTON · PI Muna I. Naash · 2023 to 2026
$1.7M
Mechanism of photoreceptor cell degeneration in animal models of retinal diseasesR56EY010609 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI NAASH, MUNA I. · 2008 to 2008
$479k
The role of ADAM9 in retinal health and diseaseK99EY033763 · NEI · DUKE UNIVERSITY · PI LEWIS, TYLOR ROBERT · 2022 to 2023
$252k
PHOTORECEPTORSR55EY010609 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI NAASH, MUNA I · 1994 to 1994
–
NEI NIH HHS K99 EY033763NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY010609NEI NIH HHS R01 EY030451NEI NIH HHS R01 EY034671NEI NIH HHS R56 EY010609U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY005722U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY010609U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY030451U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY033763U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY034671
6 · The paper itself

Abstract

Given the absence of approved treatments for pathogenic variants in Peripherin-2 (PRPH2), it is imperative to identify a universally effective therapeutic target for PRPH2 pathogenic variants. To test the hypothesis that formation of the elongated discs in presence of PRPH2 pathogenic variants is due to the presence of the full complement of rhodopsin in absence of the required amounts of functional PRPH2. Here we demonstrate the therapeutic potential of reducing rhodopsin levels in ameliorating disease phenotype in knockin models for p.Lys154del (c.458-460del) and p.Tyr141Cys (c.422 A > G) in PRPH2. Reducing rhodopsin levels improves physiological function, mitigates the severity of disc abnormalities, and decreases retinal gliosis. Additionally, intravitreal injections of a rhodopsin-specific antisense oligonucleotide successfully enhance the physiological function of photoreceptors and improves the ultrastructure of discs in mutant mice. Presented findings shows that reducing rhodopsin levels is an effective therapeutic strategy for the treatment of inherited retinal degeneration associated with PRPH2 pathogenic variants.

Indexed as

PeripherinsRhodopsinAnimalsDisease Models, AnimalDown-RegulationFemaleGene Knock-In TechniquesHumansMaleMiceMice, Inbred C57BLMutationOligonucleotides, AntisenseRetinaRetinal DegenerationRetinal DiseasesOligonucleotides, AntisensePeripherinsPRPH2 protein, humanPrph2 protein, mouseRhodopsin

Identifiers

PMID38834544
PMCPMC11150396

What OpenQuestion holds

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Registered trials

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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.