Evidence map›Paper›PMID 37445820›Full record

ArticleInternational journal of molecular sciences2023

3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina.

Yehonatan Weinberger, Ivan Budnik, Yael Nisgav, Dahlia Palevski, Gil Ben-David, José A Fernández, Shany Nivinsky Margalit, Sarina Levy-Mendelovich, Gili Kenet, Dov Weinberger and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. 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
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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Platelets at the intersection of inflammation and coagulation in the APC-mediated response to myocardial ischemia/reperfusion injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Review
  4. Article
  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

12 authors at 4 institutions in 2 countries.

Yehonatan WeinbergerRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.ORCID 0000-0002-5923-769X
Ivan BudnikDepartment of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Yael NisgavRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.
Dahlia PalevskiRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.ORCID 0000-0001-9661-5680
Gil Ben-DavidRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.ORCID 0000-0001-9993-1005
José A FernándezDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-0804-1865
Shany Nivinsky MargalitRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.
Sarina Levy-MendelovichFaculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel.ORCID 0000-0003-3971-0336
Gili KenetFaculty of Medicine, Tel Aviv University, Tel-Aviv 6997801, Israel.ORCID 0000-0003-3494-9823
Dov WeinbergerRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.
John H GriffinDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tami LivnatRabin Medical Center, Ophthalmology Department and Laboratory of Eye Research Felsenstein Medical Research Center, Petah-Tikva 5251108, Israel.ORCID 0000-0002-1279-2557
Tel Aviv University · ILRabin Medical Center · ILScripps Research Institute · USUniversity of Iowa · US

Funding

Regulation of Protein C PathwaysR01HL142975 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H, MOSNIER, LAURENT OLIVIER · 2018 to 2025
$7.3M
NHLBI NIH HHS R01 HL142975
6 · The paper itself

Abstract

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.

Indexed as

Choroidal NeovascularizationProtein CAnimalsDisease Models, AnimalInflammasomesMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinRetinaVascular Endothelial Growth Factor AInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinProtein CVascular Endothelial Growth Factor Aactivated protein Cchoroidal neovascularizationinflammation NLRP3microglia

Identifiers

PMID37445820
PMCPMC10341424
OpenAlexW4382134739

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.