Evidence map›Paper›PMID 33257736›Full record

ArticleScientific reports2020

Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy.

Santiago Delgado-Tirado, Dhanesh Amarnani, Guannan Zhao, Elizabeth J Rossin, Dean Eliott, John B Miller, Whitney A Greene, Leslie Ramos, Said Arevalo-Alquichire, David Leyton-Cifuentes and 10 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Methotrexate as an adjunct to pars plana vitrectomy for the prevention and treatment of proliferative vitreoretinopathy in rhegmatogenous retinal detachment: A clinical study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  16. Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023
    Review
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  18. The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023
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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

20 authors at 8 institutions in 3 countries.

Santiago Delgado-TiradoSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Dhanesh AmarnaniSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Guannan ZhaoSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Elizabeth J RossinRetina Service, Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Dean EliottRetina Service, Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
John B MillerRetina Service, Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Whitney A GreeneSensory Trauma Task Area, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, USA.
Leslie RamosSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Said Arevalo-AlquichireSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
David Leyton-CifuentesSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Lucia Gonzalez-BuendiaSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Daniela Isaacs-BernalSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Hannah A B WhitmoreSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Natalia ChmielewskaSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Brandon V DuffySchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Eric KimSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA.
Heuy-Ching WangSensory Trauma Task Area, United States Army Institute of Surgical Research, Fort Sam Houston, San Antonio, USA.
Jose M Ruiz-MorenoDepartment of Ophthalmology, Castilla La Mancha University, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain.
Leo A KimSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA. Leo_Kim@meei.harvard.edu.
Joseph F Arboleda-VelasquezSchepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, USA. Joseph_Arboleda@meei.harvard.edu.
Harvard University · USMassachusetts Eye and Ear Infirmary · USSmith-Kettlewell Eye Research Institute · USUnited States Army Institute of Surgical Research · USBoston College · USEIA University · COMiranza · ESUniversidad de La Sabana · CO

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
Role of Runx1 in Pathologic Ocular AngiogenesisR01EY027739 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI KIM, LEO A · 2018 to 2022
$2.8M
NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY027739NEI NIH HHS R01EY027739
6 · The paper itself

Abstract

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment surgery failure. Despite significant advances in vitreoretinal surgery, it still remains without an effective prophylactic or therapeutic medical treatment. After ocular injury or retinal detachment, misplaced retinal cells undergo epithelial to mesenchymal transition (EMT) to form contractile membranes within the eye. We identified Runt-related transcription factor 1 (RUNX1) as a gene highly expressed in surgically-removed human PVR specimens. RUNX1 upregulation was a hallmark of EMT in primary cultures derived from human PVR membranes (C-PVR). The inhibition of RUNX1 reduced proliferation of human C-PVR cells in vitro, and curbed growth of freshly isolated human PVR membranes in an explant assay. We formulated Ro5-3335, a lipophilic small molecule RUNX1 inhibitor, into a nanoemulsion that when administered topically curbed the progression of disease in a novel rabbit model of mild PVR developed using C-PVR cells. Mass spectrometry analysis detected 2.67 ng/mL of Ro5-3335 within the vitreous cavity after treatment. This work shows a critical role for RUNX1 in PVR and supports the feasibility of targeting RUNX1 within the eye for the treatment of an EMT-mediated condition using a topical ophthalmic agent.

Indexed as

Vitreoretinopathy, ProliferativeAdultAgedAnimalsCore Binding Factor Alpha 2 SubunitDisease Models, AnimalEmulsionsEpithelial-Mesenchymal TransitionFemaleGene Expression RegulationHumansMaleRabbitsCore Binding Factor Alpha 2 SubunitEmulsionsRUNX1 protein, human

Identifiers

PMID33257736
PMCPMC7705016
OpenAlexW3110417472

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.