Evidence map›Paper›PMID 27443501›Full record

ArticleExperimental eye research2017

Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury.

Peter X Shaw, Alan Sang, Yan Wang, Daisy Ho, Christopher Douglas, Lara Dia, Jeffrey L Goldberg

Abstract read
In one paragraph

Article in Experimental eye research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

35 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Article
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  7. Review
  8. Article
  9. The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  10. Article
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  18. [Rho kinase inhibitors as new local therapy option in primary open angle glaucoma].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2021
    Review
  19. Article
  20. New perspectives of immunomodulation and neuroprotection in glaucoma.Central-European journal of immunology · 2021
    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

7 authors.

Peter X ShawDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Alan SangDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Yan WangDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Daisy HoDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Christopher DouglasDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Lara DiaDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States.
Jeffrey L GoldbergDepartment of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093, United States; Byers Eye Institute, Stanford University, Palo Alto, CA 94303, United States. Electronic address: jlgoldbe@stanford.edu.

Funding

Signaling Scaffolds and Survival in StrokeR01EY022129 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GOLDBERG, JEFFREY L, KAPILOFF, MICHAEL SETH · 2012 to 2015
$2.3M
HTRA1 as a Therapeutic Target in the Treatment of Wet AMDR01EY025693 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAW, PETER X · 2015 to 2019
$1.8M
NEI NIH HHS R01 EY022129NEI NIH HHS R01 EY025693
6 · The paper itself

Abstract

Intraocular pressure (IOP)-lowering ophthalmic solutions that inhibit Rho-associated protein kinases (Rock) and norepinephrine transporters (Net) are currently under clinical evaluation. Here we evaluate topical application of one such drug for its effects on retinal ganglion cell (RGC) survival and axon regeneration after optic nerve crush injury. We performed unilateral optic nerve crush on young rats (P18) and topically applied Rock/Net inhibitor AR-13324 or placebo 3 times a day for 14 days. IOP was measured starting 3 days before and up to 9 days after injury. On day 12, cholera toxin B (CTB) was injected intravitreally to trace optic nerve regeneration. On day 14, retinas and optic nerves were collected. The retinas were flat-mounted and stained with RBPMS to quantify RGC survival and the optic nerves were sectioned for optic nerve axon quantification using fluorescent and confocal microscopy. Rock phosphorylation targets implicated in axon growth including cofilin and LIMK were examined by fluorescence microscopy and quantitative western blotting. AR-13324 lowered IOP as expected. RGC survival and optic nerve axon regeneration were significantly higher with Rock/Net inhibitor treatment compared with placebo. Furthermore, topical therapy decreased Rock target protein phosphorylation in the retinas and proximal optic nerves. These data suggest that topical administration of a Rock/Net inhibitor promotes RGC survival and regeneration after optic nerve injury, with associated molecular changes indicative of posterior drug activity. Coordinated IOP lowering and neuroprotective or regenerative effects may be advantageous in the treatment of patients with glaucoma.

Indexed as

Administration, TopicalAnimalsAxonsBenzoatesbeta-AlanineBlotting, WesternCell SurvivalDisease Models, AnimalFemaleGlaucomaImmunohistochemistryIntraocular PressureMaleNerve CrushNerve RegenerationNorepinephrine Plasma Membrane Transport ProteinsBenzoatesbeta-AlaninenetarsudilNorepinephrine Plasma Membrane Transport ProteinsOphthalmic Solutionsrho-Associated KinasesGlaucomaOptic nerveRegenerationRho-kinase

Identifiers

PMID27443501
PMCPMC5821900

What OpenQuestion holds

Textmetadata
LicenceTDM
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.