Evidence map›Paper›PMID 25151301›Full record

ReviewExperimental eye research2014

Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland.

Julie Sanderson, Darlene A Dartt, Vickery Trinkaus-Randall, Jesus Pintor, Mortimer M Civan, Nicholas A Delamere, Erica L Fletcher, Thomas E Salt, Antje Grosche, Claire H Mitchell

Open access · hybridAbstract readReview
In one paragraph

Review in Experimental eye research, 2014. 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
12.3field-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, 124 citations in OpenAlex.

  1. A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2016
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  16. Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.Investigative ophthalmology & visual science · 2022
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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

10 authors at 8 institutions in 4 countries.

Julie SandersonSchool of Pharmacy, University of East Anglia, Norwich, UK.
Darlene A DarttSchepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Vickery Trinkaus-RandallDepartment of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Jesus PintorDepartment of Biochemistry, Faculty of Optometry, Universidad Complutense de Madrid, Madrid, Spain.
Mortimer M CivanDepartment of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Nicholas A DelamereDepartment of Physiology, University of Arizona, Tucson, AZ, USA; Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
Erica L FletcherDepartment of Anatomy and of Neuroscience, University of Melbourne, Victoria, Australia.
Thomas E SaltDepartment of Visual Neuroscience, UCL Institute of Ophthalmology, London, UK.
Antje GroscheInstitute of Human Genetics, Franz-Josef-Strauß-Allee, Regensburg, Germany.
Claire H MitchellDepartment of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: chm@exchange.upenn.edu.
University of Pennsylvania · USBoston University · USMassachusetts Eye and Ear Infirmary · USUniversidad Complutense de Madrid · ESUniversity College London · GBUniversity of Arizona · USUniversity of East Anglia · GBUniversity of Melbourne · AU

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
TRPV4 as a remote controller of lens functionR01EY009532 · NEI · UNIVERSITY OF LOUISVILLE · PI DELAMERE, NICHOLAS A · 1993 to 2024
$8.0M
Molecular Mechanisms of corneal wound repairR01EY006000 · NEI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI TRINKAUS-RANDALL, VICKERY E · 1986 to 2018
$6.8M
Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
MECHANISM OF LACRIMAL GLAND SECRETIONR01EY006177 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI DARTT, DARLENE A · 1985 to 2012
$5.7M
Aqueous Humor Outflow Control and Intraocular PressureR01EY013624 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CIVAN, MORTIMER MORDECAI · 2001 to 2013
$5.6M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
SOLUTE TRANSPORT MECHANISMS IN THE CILIARY BODYR01EY006915 · NEI · UNIVERSITY OF LOUISVILLE · PI DELAMERE, NICHOLAS A · 1986 to 2013
$2.8M
EVALUATION OF TULP1 IN THE RETINAF32EY006915 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI HAGSTROM, STEPHANIE A · 1998 to 2000
$32k
NEI NIH HHS EY006177NEI NIH HHS EY009532NEI NIH HHS EY013434NEI NIH HHS EY013624NEI NIH HHS EY015537NEI NIH HHS EY01583NEI NIH HHS EY06000NEI NIH HHS EY06000SNEI NIH HHS EY06915NEI NIH HHS F32 EY006915NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY006000NEI NIH HHS R01 EY006177NEI NIH HHS R01 EY006915NEI NIH HHS R01 EY009532NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY013624NEI NIH HHS R01 EY015537
6 · The paper itself

Abstract

This review highlights recent findings that describ how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca(2+) concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease.

Indexed as

AnimalsAstrocytesCorneaEpendymoglial CellsEyeEye DiseasesHumansLacrimal ApparatusLens, CrystallinePurine NucleosidesPurine NucleotidesRetinal NeuronsRetinal Pigment EpitheliumSignal TransductionTrabecular MeshworkPurine NucleosidesPurine NucleotidesadenosineATPcorneadiadenosine polyphosphateseyelacrimal glandlensneurotransmitterP2XP2YretinaRPEtrabecular meshwork

Identifiers

PMID25151301
PMCPMC4175147
OpenAlexW2089028908

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.