Evidence map›Paper›PMID 27653972›Full record

ArticleScientific reports2016

24(S)-Hydroxycholesterol protects the ex vivo rat retina from injury by elevated hydrostatic pressure.

Makoto Ishikawa, Takeshi Yoshitomi, Charles F Zorumski, Yukitoshi Izumi

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
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  5. Oxysterols in Central and Peripheral Synaptic Communication.Advances in experimental medicine and biology · 2024
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  7. Challenges and Opportunities in P450 Research on the Eye.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations.Frontiers in cell and developmental biology · 2022
    Review
  13. Article
  14. Oxysterols Modulate the Acute Effects of Ethanol on HippocampalThe Journal of pharmacology and experimental therapeutics · 2021
    Article
  15. Article
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  18. 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

4 authors at 3 institutions in 2 countries.

Makoto IshikawaDepartment of Ophthalmology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Takeshi YoshitomiDepartment of Ophthalmology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Charles F ZorumskiThe Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, M.O., USA.
Yukitoshi IzumiThe Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, M.O., USA.
Akita University · JPTaylor Family Institute for Innovative Psychiatric ResearchWashington University in St. Louis · US

Funding

MODULATION OF HIPPOCAMPAL SYNAPTIC PLASTICITYR01MH077791 · NIMH · WASHINGTON UNIVERSITY · PI ZORUMSKI, CHARLES F · 2007 to 2013
$2.4M
Oxysterols and NMDAR FunctionR01MH101874 · NIMH · WASHINGTON UNIVERSITY · PI MENNERICK, STEVEN J, ZORUMSKI, CHARLES F · 2014 to 2018
$1.9M
NIMH NIH HHS R01 MH077791NIMH NIH HHS R01 MH101874
6 · The paper itself

Abstract

In the central nervous system, 24(S)-hydroxycholesterol (24(S)-HC) is an oxysterol synthesized from cholesterol by cholesterol 24-hydroxylase (CYP46A1) encoded by the cyp46a1 gene. In the present study using a rat ex vivo glaucoma model, we found that retinal 24(S)-HC synthesis is facilitated by pressure elevation. Moreover, we found that 24(S)-HC is neuroprotective against pressure mediated retinal degeneration. Quantitative real-time RT-PCR, ELISA, and immunohistochemistry revealed that elevated pressure facilitated the expression of cyp46a1 and CYP46A1. Immunohistochemically, the enhanced expression of CYP46A1 was mainly observed in retinal ganglion cells (RGC). LC-MS/MS revealed that 24(S)-HC levels increased in a pressure-dependent manner. Axonal injury and apoptotic RGC death induced by 75 mmHg high pressure was ameliorated by exogenously administered 1 μM 24(S)-HC. In contrast, voriconazole, a CYP46A1 inhibitor, was severely toxic even at normobaric pressure. Under normobaric conditions, 30 μM 24(S)-HC was required to prevent the voriconazole-mediated retinal damage. Taken together, our findings indicate that 24(S)-HC is facilitated by elevated pressure and plays a neuroprotective role under glaucomatous conditions, while voriconazole, an antifungal drug, is retinotoxic. 24(S)-HC and related compounds may serve as potential therapeutic targets for protecting glaucomatous eyes from pressure-induced injuries.

Identifiers

PMID27653972
PMCPMC5032171
OpenAlexW2523363359

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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.