Evidence map›Paper›PMID 30025125›Full record

ArticleInvestigative ophthalmology & visual science2018

D-cis-Diltiazem Can Produce Oxidative Stress in Healthy Depolarized Rods In Vivo.

Bruce A Berkowitz, Robert H Podolsky, Benjamin Farrell, Hojun Lee, Christopher Trepanier, Ali M Berri, Kristin Dernay, Emma Graffice, Fatema Shafie-Khorassani, Timothy S Kern and 1 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  6. Article
  7. OCT imaging of rod mitochondrial respirationExperimental biology and medicine (Maywood, N.J.) · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Rod Photoreceptor Neuroprotection in Dark-Reared Pde6brd10 Mice.Investigative ophthalmology & visual science · 2020
    Article
  14. Review
  15. Article
  16. 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

11 authors at 3 institutions in 1 country.

Bruce A BerkowitzDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Robert H PodolskyDepartment of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States.
Benjamin FarrellDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Hojun LeeDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Christopher TrepanierDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Ali M BerriDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Kristin DernayDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Emma GrafficeDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Fatema Shafie-KhorassaniDepartment of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States.
Timothy S KernDepartment of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
Robin RobertsDepartment of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States.
Wayne State University · USMichigan United · USCase Western Reserve University · US

Funding

VISION RESEARCH--COREP30EY004068 · NEI · WAYNE STATE UNIVERSITY · PI LINDA D HAZLETT · 1985 to 2026
$13.2M
Novel therapies to inhibit Diabetic RetinopathyR24EY024864 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KERN, TIMOTHY S · 2015 to 2019
$8.1M
Role of Photoreceptors in the Pathogenesis of Diabetic RetinopathyR01EY022938 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KERN, TIMOTHY S · 2013 to 2021
$3.7M
Novel Imaging Biomarker for Treating Spatial Memory Loss in Prodromal Alzheimer's Disease ModelsR01AG058171 · NIA · WAYNE STATE UNIVERSITY · PI BENNETT, BRIAN M, BERKOWITZ, BRUCE A. · 2017 to 2021
$2.8M
Novel Imaging of rod oxidative stress in retinal disease and treatment in vivoR01EY026584 · NEI · WAYNE STATE UNIVERSITY · PI BERKOWITZ, BRUCE A. · 2016 to 2019
$1.5M
NEI NIH HHS P30 EY004068NEI NIH HHS R01 EY022938NEI NIH HHS R01 EY026584NEI NIH HHS R24 EY024864NIA NIH HHS R01 AG058171
6 · The paper itself

Abstract

Purpose: New perspectives are needed to understand decades of contradictory reports on the neuroprotective effects of the Cav1.2 L-type calcium channel blocker d-cis-diltiazem in retinitis pigmentosa (RP) models. Here, we address, in vivo, the following two knowledge gaps regarding d-cis-diltiazem's actions in the murine outer retina: (1) do normal mouse rods contain d-cis-diltiazem-insensitive Cav1.2 L-type calcium channels? (2) Can d-cis-diltiazem modify the normal rod redox environment? Methods: First, transretinal Cav1.2 L-type calcium channels were noninvasively mapped with manganese-enhanced magnetic resonance imaging (MRI) following agonist Bay K 8644 in C57BL/6 (B6) and in Cav1.2 L-type calcium channel BAY K 8644-insensitive mutant B6 mice. Second, d-cis-diltiazem-treated oxidative stress-vulnerable (B6) or -resistant [129S6 (S6)] mice were examined in vivo (QUEnch-assiSTed [QUEST] MRI) and in whole retina ex vivo (lucigenin). Retinal thickness was measured using MRI. Results: The following results were observed: (1) manganese uptake patterns in BAY K 8644-treated controls and mutant mice identified in vivo Cav1.2 L-type calcium channels in inner and outer retina; and (2) d-cis-diltiazem induced rod oxidative stress in dark-adapted B6 mice but not in light-adapted B6 mice or dark-adapted S6 mice (QUEST MRI). Oxidative stress in vivo was limited to inferior outer retina in dark-adapted B6 mice approximately 1-hour post d-cis-diltiazem. By approximately 4 hours post, only superior outer retina oxidative stress was observed and whole retinal superoxide production was supernormal. All groups had unremarkable retinal thicknesses. Conclusions: D-cis-diltiazem's unexpectedly complex spatiotemporal outer retinal oxidative stress pattern in vivo was dependent on genetic background and rod membrane depolarization, but not apparently dependent on Cav1.2 L-type calcium channels, providing a potential rationale for contradictory results in different RP models.

Indexed as

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterAnimalsCalcium Channel AgonistsCalcium Channel BlockersCalcium Channels, L-TypeDark AdaptationDiltiazemMagnetic Resonance ImagingMaleMiceMice, Inbred C57BLOxidative StressRetinal DegenerationRetinal Rod Photoreceptor CellsSuperoxidesTomography, Optical Coherence3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl esterCACNA1C protein, mouseCalcium Channel AgonistsCalcium Channel BlockersCalcium Channels, L-TypeDiltiazemSuperoxides

Identifiers

PMID30025125
PMCPMC5995482
OpenAlexW2810447283

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.