Evidence map›Paper›PMID 34967831›Full record

ArticleTranslational vision science & technology2021

Topical Ketotifen Fumarate Inhibits Choroidal Mast Cell Degranulation and Loss of Retinal Pigment Epithelial Cells in Rat Model for Geographic Atrophy.

Tomohiro Nizawa, Imran A Bhutto, Anupama Tiwari, Rhonda R Grebe, Jesse Alt, Rana Rais, Malia M Edwards, Gerard A Lutty

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

Article in Translational vision science & technology, 2021. 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
0.7field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

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  5. Review
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

8 authors at 2 institutions in 1 country.

Tomohiro NizawaWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Imran A BhuttoWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anupama TiwariWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rhonda R GrebeWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jesse AltBrain Science Institute, Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rana RaisBrain Science Institute, Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Malia M EdwardsWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gerard A LuttyWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Inflammatory cells of choroid: a therapeutic target in AMD.R01EY016151 · NEI · JOHNS HOPKINS UNIVERSITY · PI EDWARDS, MALIA MICHELLE · 2006 to 2024
$8.0M
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY016151
6 · The paper itself

Abstract

Purpose: This study evaluates whether topical ketotifen fumarate (KTF) can prevent geographic atrophy (GA)-like phenotypes in a rat model. Methods: Pharmacokinetics (PKs) of KTF after topical administration twice daily for 5 days was analyzed in rat retina, retinal pigment epithelium (RPE)/choroid/sclera, and in plasma by an liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Rats were then given hydrogel implants +/- 48/80 in the superior subconjunctival space and topically treated with 1% and 0.25% of KTF or phosphate buffer saline (PBS) twice daily. Rats were euthanized at 1, 2, 4, and 8 weeks postinjection. Choroidal mast cells (MCs) were stained with nonspecific esterase and the RPE monolayer was labeled with RPE65 and ZO-1 in whole mount choroids. Retinal and choroidal areas were determined in cryosections stained with picrosirius red. Dark-adapted electroretinogram (ERG) was also performed to evaluate retinal function. Results: PK results showed the highest level of KTF (average 5.6 nM/mg) in the RPE/choroid/sclera in rats given topical 1% KTF. Topical 1% KTF significantly reduced choroidal MC degranulation at 1 week and 2 weeks (both P < 0.001) and RPE loss at 4 weeks (P < 0.001) as well as retinal and choroidal thinning (both P < 0.001) and reduction in ERG amplitude at 8 weeks (P < 0.05) compared to PBS. Similar results were obtained with 0.25% KTF. Conclusions: Both 1% and 0.25% KTF eye drops effectively reduced MC degranulation, RPE loss, and retinal and choroidal thinning while preventing the decline of ERG amplitude in a GA-like rat model. These data suggest that topical KTF might be a new therapeutic drug for treating GA. Translational Relevance: The results of this study demonstrate that topical KTF successfully reduced GA-like phenotypes in a rat model and may provide a novel therapy for GA.

Indexed as

Geographic AtrophyAnimalsCell DegranulationChoroidChromatography, LiquidEpithelial CellsKetotifenRatsRetinal PigmentsTandem Mass SpectrometryKetotifenRetinal Pigments

Identifiers

PMID34967831
PMCPMC8727493
OpenAlexW4200074368

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.