Evidence map›Paper›PMID 40378380›Full record

ArticlePloS one2025

Inhibition of VE-PTP rejuvenates Schlemm's canal in aged mice and acts via Tie2.

Sarthak Mishra, Ute Ipe, Astrid F Nottebaum, Kevin G Peters, Dietmar Vestweber

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Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

1 citing paper in PubMed.

  1. 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

5 authors.

Sarthak MishraDepartment of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.ORCID https://orcid.org/0000-0003-2817-5681
Ute IpeDepartment of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Astrid F NottebaumDepartment of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.ORCID https://orcid.org/0000-0003-2246-7851
Kevin G PetersAerpio Therapeutics, Inc., Blue Ash, Ohio, United States of America.
Dietmar VestweberDepartment of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGlaucoma is the leading cause of irreversible blindness worldwide and is associated with high intraocular pressure (IOP). Schlemm's canal (SC), a hybrid vessel present in the anterior part of the eye, is known to control IOP by draining aqueous humor into the systemic circulation. Formation and function of SC is supported by the tyrosine kinase receptor Tie2. Likewise, inhibition of the vascular endothelial protein tyrosine phosphatase (VE-PTP), which associates with Tie2 has similar effects. However, VE-PTP also targets VE-cadherin and several other substrates. Here, we analyzed whether Tie2 is indeed the major substrate which is responsible for the role of VE-PTP in SC function. In addition, we analyzed the function of VE-PTP in SC of the aged eye in mice. METHODOLOGY: We tested the effects of the VE-PTP inhibitor AKB9778 and of VE-PTP gene inactivation on SC area and IOP in WT and in Tie2iLEC/SC-KO and VE-cadherin-Y685F mutant mice.

resultsPharmacologic inhibition of VE-PTP with AKB9778 increased SC area only in mice expressing Tie2. The VE-cadherin-Y685F mutation had neither an effect on SC area nor on the effects of AKB9778 on SC formation. Induced VE-PTP gene inactivation in adult mice had similar effects as AKB9778. Furthermore, we could show that AKB9778 improved SC function in aged mice as judged by increasing SC area and lowering of IOP.

conclusionInterference with VE-PTP function improves SC function in a strictly Tie2 dependent way and pharmacologic inhibition of VE-PTP with AKB9778 is a promising approach for improving SC function in the aged eye.

Indexed as

AgingReceptor-Like Protein Tyrosine Phosphatases, Class 3Receptor, TIE-2Aniline CompoundsAnimalsAntigens, CDCadherin 5CadherinsIntraocular PressureMiceMice, Inbred C57BLMice, KnockoutSchlemm's CanalSulfonic AcidsAKB-9778Aniline CompoundsAntigens, CDCadherin 5CadherinsReceptor-Like Protein Tyrosine Phosphatases, Class 3Receptor, TIE-2Sulfonic AcidsTek protein, mouse

Identifiers

PMID40378380
PMCPMC12084045

What Socratic holds

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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 Socratic graph.