Evidence map›Paper›PMID 22916143›Full record

ArticlePloS one2012

Autotaxin-lysophosphatidic acid axis is a novel molecular target for lowering intraocular pressure.

Padma Iyer, Robert Lalane, Corey Morris, Pratap Challa, Robin Vann, Ponugoti Vasantha Rao

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

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.3field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Article
  13. Synthesis, Characterization, andFrontiers in pharmacology · 2021
    Article
  14. Article
  15. Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

6 authors at 1 institution in 1 country.

Padma IyerDepartment of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA.
Robert Lalane
Corey Morris
Pratap Challa
Robin Vann
Ponugoti Vasantha Rao
Duke University · US

Funding

NEI NIH HHS EY18950NEI NIH HHS R01 EY18950
6 · The paper itself

Abstract

Primary open-angle glaucoma is the second leading cause of blindness in the United States and is commonly associated with elevated intraocular pressure (IOP) resulting from diminished aqueous humor (AH) drainage through the trabecular pathway. Developing effective therapies for increased IOP in glaucoma patients requires identification and characterization of molecular mechanisms that regulate IOP and AH outflow. This study describes the identification and role of autotaxin (ATX), a secretory protein and a major source for extracellular lysophosphatidic acid (LPA), in regulation of IOP in a rabbit model. Quantitative proteomics analysis identified ATX as an abundant protein in both human AH derived from non-glaucoma subjects and in AH from different animal species. The lysophospholipase D (LysoPLD) activity of ATX was found to be significantly elevated (by ∼1.8 fold; n=20) in AH derived from human primary open angle glaucoma patients as compared to AH derived from age-matched cataract control patients. Immunoblotting analysis of conditioned media derived from primary cultures of human trabecular meshwork (HTM) cells has confirmed secretion of ATX and the ability of cyclic mechanical stretch of TM cells to increase the levels of secreted ATX. Topical application of a small molecular chemical inhibitor of ATX (S32826), which inhibited AH LysoPLD activity in vitro (by >90%), led to a dose-dependent and significant decrease of IOP in Dutch-Belted rabbits. Single intracameral injection of S32826 (∼2 µM) led to significant reduction of IOP in rabbits, with the ocular hypotensive response lasting for more than 48 hrs. Suppression of ATX expression in HTM cells using small-interfering RNA (siRNA) caused a decrease in actin stress fibers and myosin light chain phosphorylation. Collectively, these observations indicate that the ATX-LPA axis represents a potential therapeutic target for lowering IOP in glaucoma patients.

Indexed as

Intraocular PressureAnilidesAnimalsAqueous HumorGlaucoma, Open-AngleHumansLysophospholipase DLysophospholipidsModels, AnimalOrganophosphonatesPhosphoric Diester HydrolasesProteomicsRabbitsRNA, Small InterferingTrabecular Meshwork(4-(tetradecanoylamino)benzyl)phosphonic acidAnilideslysophosphatidic acidLysophospholipase DLysophospholipidsOrganophosphonatesPhosphoric Diester HydrolasesRNA, Small Interfering

Identifiers

PMID22916143
PMCPMC3423407
OpenAlexW1974732432

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.