Evidence map›Paper›PMID 26720461›Full record

ArticleInvestigative ophthalmology & visual science2015

Thrombomodulin Protects Against Bacterial Keratitis, Is Anti-Inflammatory, but Not Angiogenic.

Sharon A McClellan, Sandamali A Ekanayaka, Cui Li, Xiaoyu Jiang, Ronald P Barrett, Linda D Hazlett

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Topical Glycyrrhizin Is Therapeutic for Pseudomonas aeruginosa Keratitis.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018
    Article
  6. Designed Host Defense Peptides for the Treatment of Bacterial Keratitis.Investigative ophthalmology & visual science · 2017
    Article
  7. Article
  8. Article
  9. Decreasing HMGB1 levels improves outcome ofJournal of rare diseases research & treatment · 2016
    Article
  10. Challenges of corneal infections.Expert review of ophthalmology · 2016
    Article
  11. Non-antibiotic management of bacterial keratitis.Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society
    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

6 authors at 2 institutions in 1 country.

Sharon A McClellan
Sandamali A Ekanayaka
Cui Li
Xiaoyu Jiang
Ronald P Barrett
Linda D Hazlett
Wayne State University · USMichigan United · US

Funding

VISION RESEARCH--COREP30EY004068 · NEI · WAYNE STATE UNIVERSITY · PI LINDA D HAZLETT · 1985 to 2026
$13.2M
ALTERATION WITH AGE OF RESISTANCE TO EYE INFECTIONSR01EY002986 · NEI · WAYNE STATE UNIVERSITY · PI HAZLETT, LINDA D · 1985 to 2013
$6.2M
Role of Toll-Like Receptors in Bacterial KeratitisR01EY016058 · NEI · WAYNE STATE UNIVERSITY · PI HAZLETT, LINDA D · 2005 to 2023
$6.0M
NEI NIH HHS P30 EY004068NEI NIH HHS P30EY004068NEI NIH HHS R01 EY002986NEI NIH HHS R01EY002986NEI NIH HHS R01 EY016058NEI NIH HHS R01EY016058
6 · The paper itself

Abstract

purposeThrombomodulin (TM) is a multidomain, transmembrane protein with anti-inflammatory properties. Thrombomodulin domain (D) 1 is lectin-like, interacting with Lewis Y antigen on lipopolysaccharide, and with HMGB1, while TMD23 is associated with angiogenic and anti-inflammatory functions. Thus, we tested if TM is protective against Pseudomonas aeruginosa keratitis and whether it enhanced corneal vascularity.

methodsEyes of C57BL/6 (B6) mice were injected with recombinant TM (rTM), rTMD1, or PBS subconjunctivally before and intraperitoneally after infection with P. aeruginosa. Clinical scores, photography with a slit lamp, RT-PCR, ELISA, myeloperoxidase (MPO) assay, viable bacterial plate counts, and India ink perfusion were used to assess the disease response and corneal vascularity (rTM only).

resultsRecombinant TM versus PBS treatment reduced clinical scores and corneal opacity. Corneal mRNA levels for HMGB1 were unchanged, but proinflammatory molecules IL-1β, CXCL2, NF-κB, TLR4, and RAGE were decreased; anti-inflammatory molecules SIGIRR and ST2 were increased. ELISA confirmed the mRNA data for HMGB1, IL-1β, and CXCL2 proteins. Both neutrophil influx and viable bacterial plate counts also were decreased after rTM treatment. Protein levels for angiogenic molecules VEGF, VEGFR-1, and VEGFR-2 were measured at 5 days post infection and were not different or reduced significantly after rTM treatment. Further, perfusion with India ink revealed similar vessel ingrowth between the two groups. Similar studies were performed with rTMD1, but disease severity, mRNA, proteins, MPO, and plate counts were not changed from controls.

conclusionsThese data provide evidence that rTM treatment is protective against bacterial keratitis, does not reduce HMGB1, and is not angiogenic.

Indexed as

AnimalsAnti-Inflammatory AgentsColony Count, MicrobialCorneaCytokinesDisease Models, AnimalEnzyme-Linked Immunosorbent AssayEye Infections, BacterialKeratitisMiceMice, Inbred C57BLNeutrophilsNF-kappa BProtective AgentsPseudomonas aeruginosaPseudomonas InfectionsAnti-Inflammatory AgentsCytokinesFLT1 protein, humanNF-kappa BProtective AgentsRNA, MessengerThrombomodulinVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2

Identifiers

PMID26720461
PMCPMC5110241
OpenAlexW2346718910

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.