Evidence map›Paper›PMID 27842161›Full record

ArticleInvestigative ophthalmology & visual science2016

Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.

Ruiyi Ren, Guorong Li, Thuy Duong Le, Casey Kopczynski, W Daniel Stamer, Haiyan Gong

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
12.8field-weighted citation impact, top 1% 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

72 citing papers in PubMed, 155 citations in OpenAlex.

  1. MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
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  7. The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018
    Trial
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  13. Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.International journal of drug discovery and pharmacology · 2025
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  15. Review
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  17. Segmental Unconventional Outflow in Mouse Eyes.Investigative ophthalmology & visual science · 2023
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  19. Article
  20. Article

12 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Ruiyi RenDepartment of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States 2Department of Anatomoy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States.
Guorong LiDepartment of Ophthalmology, Duke University, Durham, North Carolina, United States.
Thuy Duong LeDepartment of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States.
Casey KopczynskiAerie Pharmaceuticals, Inc., Durham, North Carolina, United States.
W Daniel StamerDepartment of Ophthalmology, Duke University, Durham, North Carolina, United States.
Haiyan GongDepartment of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States 2Department of Anatomoy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States.
Boston University · USDuke University · USAerie Pharmaceuticals (United States) · US

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
The Mechanical Basis of Primary Open Angle GlaucomaR01EY019696 · NEI · NORTHWESTERN UNIVERSITY · PI FREDBERG, JEFFREY J, JOHNSON, MARK · 2009 to 2019
$7.6M
Cellular Physiology of the Aqueous Outflow PathwayR01EY022634 · NEI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GONG, HAIYAN · 2012 to 2020
$3.7M
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY019696NEI NIH HHS R01 EY022634
6 · The paper itself

Abstract

purposeNetarsudil is a Rho kinase/norepinephrine transporter inhibitor currently in phase 3 clinical development for glaucoma treatment. We investigated the effects of its active metabolite, netarsudil-M1, on outflow facility (C), outflow hydrodynamics, and morphology of the conventional outflow pathway in enucleated human eyes.

methodsPaired human eyes (n = 5) were perfused with either 0.3 μM netarsudil-M1 or vehicle solution at constant pressure (15 mm Hg). After 3 hours, fluorescent microspheres were added to perfusion media to trace the outflow patterns before perfusion-fixation. The percentage effective filtration length (PEFL) was calculated from the measured lengths of tracer distribution in the trabecular meshwork (TM), episcleral veins (ESVs), and along the inner wall (IW) of Schlemm's canal after global and confocal imaging. Morphologic changes along the trabecular outflow pathway were investigated by confocal, light, and electron microscopy.

resultsPerfusion with netarsudil-M1 significantly increased C when compared to baseline (51%, P < 0.01) and to paired controls (102%, P < 0.01), as well as significantly increased PEFL in both IW (P < 0.05) and ESVs (P < 0.01). In treated eyes, PEFL was significantly higher in ESVs than in the IW (P < 0.01) and was associated with increased cross-sectional area of ESVs (P < 0.01). Percentage effective filtration length in ESVs positively correlated with the percentage change in C (R2 = 0.58, P = 0.01). A significant increase in juxtacanalicular connective tissue (JCT) thickness (P < 0.05) was found in treated eyes compared to controls.

conclusionsNetarsudil acutely increased C by expansion of the JCT and dilating the ESVs, which led to redistribution of aqueous outflow through a larger area of the IW and ESVs.

Indexed as

AdultAgedAqueous HumorCadaverHumansIntraocular PressureMicroscopy, ConfocalMicroscopy, ElectronMiddle AgedNorepinephrine Plasma Membrane Transport ProteinsPerfusionrho-Associated KinasesTrabecular MeshworkNorepinephrine Plasma Membrane Transport Proteinsrho-Associated KinasesSLC6A2 protein, human

Identifiers

PMID27842161
PMCPMC5114035
OpenAlexW2556991392

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.