Evidence map›Paper›PMID 36255358›Full record

ArticleTranslational vision science & technology2022

Direct Tie2 Agonists Stabilize Vasculature for the Treatment of Diabetic Macular Edema.

Nicholas J Agard, Gu Zhang, John Ridgeway, Danielle M Dicara, Phillip Y Chu, Rachana Ohri, Sarah Sanowar, Jean-Michel Vernes, Hannah Chi, Jiameng Zhang and 23 more

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

Article in Translational vision science & technology, 2022. 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
2.0field-weighted citation impact, top 14% 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, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. 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

33 authors.

Nicholas J AgardGenentech Research and Early Development, South San Francisco, CA, USA.
Gu ZhangGenentech Research and Early Development, South San Francisco, CA, USA.
John RidgewayGenentech Research and Early Development, South San Francisco, CA, USA.
Danielle M DicaraGenentech Research and Early Development, South San Francisco, CA, USA.
Phillip Y ChuGenentech Research and Early Development, South San Francisco, CA, USA.
Rachana OhriGenentech Research and Early Development, South San Francisco, CA, USA.
Sarah SanowarGenentech Research and Early Development, South San Francisco, CA, USA.
Jean-Michel VernesGenentech Research and Early Development, South San Francisco, CA, USA.
Hannah ChiGenentech Research and Early Development, South San Francisco, CA, USA.
Jiameng ZhangGenentech Research and Early Development, South San Francisco, CA, USA.
Emily HolzGenentech Research and Early Development, South San Francisco, CA, USA.
Maciej PaluchGenentech Research and Early Development, South San Francisco, CA, USA.
Guannan HeGenentech Research and Early Development, South San Francisco, CA, USA.
Yingjia BensonGenentech Research and Early Development, South San Francisco, CA, USA.
Jianhuan ZhangGenentech Research and Early Development, South San Francisco, CA, USA.
Pamela ChanGenentech Research and Early Development, South San Francisco, CA, USA.
Nga TangGenentech Research and Early Development, South San Francisco, CA, USA.
Prachi JavaleGenentech Research and Early Development, South San Francisco, CA, USA.
Blair WilsonGenentech Research and Early Development, South San Francisco, CA, USA.
Kathy BarrettGenentech Research and Early Development, South San Francisco, CA, USA.
Rebecca K RowntreeGenentech Research and Early Development, South San Francisco, CA, USA.
Julie HangGenentech Research and Early Development, South San Francisco, CA, USA.
Y Gloria MengGenentech Research and Early Development, South San Francisco, CA, USA.
Phil HassGenentech Research and Early Development, South San Francisco, CA, USA.
Germaine FuhGenentech Research and Early Development, South San Francisco, CA, USA.
Robert PiskolGenentech Research and Early Development, South San Francisco, CA, USA.
Vladimir BantseevGenentech Research and Early Development, South San Francisco, CA, USA.
Kelly M LoyetGenentech Research and Early Development, South San Francisco, CA, USA.
John C TranGenentech Research and Early Development, South San Francisco, CA, USA.
Cong WuGenentech Research and Early Development, South San Francisco, CA, USA.
Vahan B IndjeianGenentech Research and Early Development, South San Francisco, CA, USA.
Vittal ShivvaGenentech Research and Early Development, South San Francisco, CA, USA.
Minhong YanGenentech Research and Early Development, South San Francisco, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients. Methods: We explored direct agonists of Tie2, a receptor known to stabilize vasculature and prevent leakage. We identified a multivalent PEG-Fab conjugate, Tie2.1-hexamer, that oligomerizes Tie2 and drives receptor activation and characterized its activities in vitro and in vivo. Results: Tie2.1-hexamer normalized and stabilized intercellular junctions of stressed endothelial cell monolayers in vitro, suppressed vascular leak in mice under conditions where anti-VEGF alone was ineffective, and demonstrated extended ocular exposure and robust pharmacodynamic responses in non-human primates. Conclusions: Tie2.1-hexamer directly activates the Tie2 pathway, reduces vascular leak, and is persistent within the vitreal humor. Translational Relevance: Our study presents a promising potential therapeutic for the treatment of DME.

Indexed as

Diabetes MellitusDiabetic RetinopathyMacular EdemaAnimalsBlindnessEndothelial Growth FactorsMiceVision DisordersVisual AcuityEndothelial Growth Factors

Identifiers

PMID36255358
PMCPMC9587485
OpenAlexW4306730932

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.