Evidence map›Paper›PMID 18326723›Full record

ArticleInvestigative ophthalmology & visual science2008

Disruption of CFTR-dependent lipid rafts reduces bacterial levels and corneal disease in a murine model of Pseudomonas aeruginosa keratitis.

Tanweer Zaidi, Milan Bajmoczi, Tauqeer Zaidi, David E Golan, Gerald B Pier

Open access · greenAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.7field-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

26 citing papers in PubMed, 45 citations in OpenAlex.

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  10. The Role ofPathogens (Basel, Switzerland) · 2019
    Review
  11. Repair Process Impairment byFrontiers in cellular and infection microbiology · 2019
    Review
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  13. Article
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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

5 authors at 1 institution in 1 country.

Tanweer ZaidiChanning Laboratory and Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Milan Bajmoczi
Tauqeer Zaidi
David E Golan
Gerald B Pier
Brigham and Women's Hospital · US

Funding

Pathogensis of Bacterial corneal infectionR01EY016144 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI PIER, GERALD B · 2005 to 2018
$5.6M
Molecular Interactions in Erythroid Cell MembranesR37HL032854 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GOLAN, DAVID E. · 1997 to 2006
$3.0M
Molecular Regulation of Adhesive Integrin Interactions in Erythroblastic IslandsR01HL032854 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GOLAN, DAVID E. · 1985 to 2011
$2.0M
NEI NIH HHS EY016144NEI NIH HHS R01 EY016144NHLBI NIH HHS HL32854NHLBI NIH HHS R01 HL032854NHLBI NIH HHS R37 HL032854
6 · The paper itself

Abstract

purposePseudomonas aeruginosa enters corneal epithelial cells in vitro via membrane microdomains or lipid rafts. Bacterial entry, mediated by the cystic fibrosis transmembrane conductance regulator (CFTR), promotes infection and disease. This study was conducted to determine whether P. aeruginosa and CFTR are colocalized to rafts in isogenic corneal cells expressing wild-type (WT) or mutant DeltaF508-CFTR and whether disruption of the rafts both in vitro and in vivo affects the bacterial levels and the course of the disease.

methodsTransformed human corneal epithelial cells from a patient homozygous for DeltaF508-CFTR, and the same cells corrected with WT-CFTR, were exposed to six isolates of P. aeruginosa-three invasive and three cytotoxic strains-in the presence of beta-cyclodextrin (CD), which disrupts rafts. Association and cellular uptake of the invasive strains were measured, as was lactate dehydrogenase release induced by the cytotoxic strains. Scratch-injured mouse eyes were infected with the six P. aeruginosa strains, and the effect of prophylactic or therapeutic administration of CD on bacterial levels and disease was evaluated.

resultsP. aeruginosa and CFTR were colocalized with lipid rafts in cells with WT-CFTR, and CD treatment of these cells disrupted bacterial association, internalization, and cytotoxic effects. Cells expressing DeltaF508-CFTR were marginally affected by CD. Prophylactic and therapeutic topical application of CD ameliorated corneal disease and reduced the bacterial count in the eye.

conclusionsP. aeruginosa enters human corneal epithelial cells via lipid rafts containing CFTR, and disruption of raft-mediated uptake of this organism by CD protects against disease and reduces bacterial levels in the mouse model of keratitis.

Indexed as

AnimalsBacterial Adhesionbeta-CyclodextrinsBlotting, WesternCell Line, TransformedColony Count, MicrobialCorneal UlcerCystic Fibrosis Transmembrane Conductance RegulatorDisease Models, AnimalEpithelium, CornealEye Infections, BacterialFluorescent Antibody TechniqueHumansMembrane MicrodomainsMiceMicroscopy, Confocalbeta-CyclodextrinsCystic Fibrosis Transmembrane Conductance RegulatorRNA, Small Interfering

Identifiers

PMID18326723
PMCPMC2279184
OpenAlexW2035296599

What OpenQuestion holds

Textmetadata
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.