Evidence map›Paper›PMID 39167399›Full record

ArticleInvestigative ophthalmology & visual science2024

Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.

Ryo Terao, Brian S Sohn, Taku Yamamoto, Tae Jun Lee, Jason Colasanti, Charles W Pfeifer, Joseph B Lin, Andrea Santeford, Shinobu Yamaguchi, Mitsukuni Yoshida and 1 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
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  3. Review
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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

11 authors.

Ryo TeraoJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Brian S SohnJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Taku YamamotoJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Tae Jun LeeJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Jason ColasantiJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Charles W PfeiferJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Joseph B LinJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Andrea SantefordJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Shinobu YamaguchiJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Mitsukuni YoshidaJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Rajendra S ApteJohn F. Hardesty, MD, Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.

Funding

NATIONAL RESEARCH SERVICE AWARD-MEDICAL SCIENTISTT32GM007200 · NIGMS · WASHINGTON UNIVERSITY · PI YOKOYAMA, WAYNE M. · 1985 to 2024
$59.8M
WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Steven Bassnett · 1985 to 2026
$18.4M
Research Training Program in the Vision SciencesT32EY013360 · NEI · WASHINGTON UNIVERSITY · PI SHIMING CHEN, Daniel Kerschensteiner · 2000 to 2026
$5.6M
Role of stearoyl-CoA desaturase 2 in macrophage-mediated antimicrobial immunityF30DK130282 · NIDDK · WASHINGTON UNIVERSITY · PI LIN, JOSEPH B · 2021 to 2023
$117k
NEI NIH HHS P30 EY002687NEI NIH HHS T32 EY013360NIDDK NIH HHS F30 DK130282NIGMS NIH HHS T32 GM007200
6 · The paper itself

Abstract

Purpose: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors. Methods: Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina. Results: Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch's membrane thickening. Conclusions: Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation.

Indexed as

ATP Binding Cassette Transporter 1Cellular SenescenceCholesterolDisease Models, AnimalMice, KnockoutRetinal DegenerationAnimalsATP Binding Cassette Transporter, Subfamily G, Member 1MiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionRetinal Rod Photoreceptor CellsAbca1 protein, mouseABCG1 protein, mouseATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1Cholesterol

Identifiers

PMID39167399
PMCPMC11343002

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.