Evidence map›Paper›PMID 19136711›Full record

ArticleInvestigative ophthalmology & visual science2009

In situ fluorescence measurement of tear film [Na+], [K+], [Cl-], and pH in mice shows marked hypertonicity in aquaporin-5 deficiency.

Javier Ruiz-Ederra, Marc H Levin, A S Verkman

Open access · greenAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

29 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Non-contact confocal calcium imaging ofBiomedical optics express · 2025
    Article
  6. Article
  7. Elucidating the roles of electrolytes and hydrogen bonding in the dewetting dynamics of the tear film.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Review
  9. Aquaporins in the Cornea.International journal of molecular sciences · 2024
    Review
  10. Ion channels in dry eye disease.Indian journal of ophthalmology · 2023
    Review
  11. Aquaporins in Glandular Secretion.Advances in experimental medicine and biology · 2023
    Article
  12. Ocular Surface Ion Transport and Dry Eye Disease.Current ophthalmology reports · 2022
    Article
  13. Review
  14. Topical administration of ambroxol eye drops augments tear secretion in rabbits.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021
    Article
  15. Review
  16. Article
  17. Article
  18. Experimental Pharmacotherapy for Dry Eye Disease: A Review.Journal of experimental pharmacology · 2021
    Review
  19. Article
  20. Ions, the Movement of Water and the Apoptotic Volume Decrease.Frontiers in cell and developmental biology · 2020
    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

3 authors at 1 institution in 1 country.

Javier Ruiz-EderraDepartment of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Marc H Levin
A S Verkman
University of California, San Francisco · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAKKARAJU, APARNA · 1985 to 2024
$16.8M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
Application of Novel Optical Methods to Cell DynamicsR37EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2007 to 2016
$4.1M
Role of ASL and Airway Glands in CF Lung DiseaseR01HL073856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2003 to 2010
$3.1M
PHYSIOLOGY AND MOLECULAR BIOLOGY OF LUNG WATER TRANSPORTR01HL059198 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1998 to 2007
$2.2M
Application of Novel Optical Methods to Cell DynamicsR01EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2006
$1.7M
WATER AND NON-ELECTROLYTE TRANSPORT IN RENAL VESICLESR01DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1986 to 2014
$1.4M
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NHLBI NIH HHS HL59198NHLBI NIH HHS HL73856NHLBI NIH HHS R01 HL059198NHLBI NIH HHS R01 HL073856NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK72517NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124
6 · The paper itself

Abstract

purposeTear film composition depends on water and ion transport across ocular surface epithelia and on fluid secretion by lacrimal glands. The purpose of this study was to establish in situ fluorescence methods to measure tear film ionic concentrations and pH in mice and to determine whether tear film composition is sensitive to deficiency of the major ocular surface aquaporin water channels.

methodsTear film ionic concentrations and pH were measured in anesthetized mice by ratio imaging fluorescence microscopy after topical application of ion/pH-sensing, dual-wavelength fluorescent indicators. [Na(+)], [K(+)], and [Cl(-)] were measured with membrane-impermeant indicators developed by our laboratory, and pH was measured with bis(carboxyethyl)-carboxyfluorescein fluorescence-conjugated dextran. Measurements were performed on wild-type mice and on knockout mice lacking aquaporins AQP1, AQP3, and AQP5.

resultsIn wild-type mice, tear film [Na(+)] was 139 +/- 8 mM, [K(+)] was 48 +/- 1 mM, [Cl(-)] was 127 +/- 4 mM, and pH was 7.59 +/- 0.2 (SE; n = 5-8). pH did not differ significantly in the AQP knockout mice. [Na(+)] was increased by approximately twofold in AQP5 null mice (230 +/- 20 mM) and was greatly reduced after exposure of the ocular surface to a humidified atmosphere. [K(+)] was mildly reduced in AQP1 null mice.

conclusionsThese results establish an in situ optical methodology to measure tear film [Na(+)], [K(+)], [Cl(-)], and pH in living mice, without the need for fluid sampling. Tear film hypertonicity in AQP5 deficiency is likely caused by reduced transcorneal water secretion in response to evaporative water loss.

Indexed as

AnimalsAquaporin 1Aquaporin 3Aquaporin 5Body WaterChloridesCorneaFluorescent DyesHydrogen-Ion ConcentrationIn Situ Hybridization, FluorescenceIon TransportMiceMice, KnockoutMicroscopy, FluorescenceOsmolar ConcentrationPotassiumAqp1 protein, mouseAqp3 protein, mouseAqp5 protein, mouseAquaporin 1Aquaporin 3Aquaporin 5ChloridesFluorescent DyesPotassiumSodium

Identifiers

PMID19136711
PMCPMC2904304
OpenAlexW1972396641

What OpenQuestion holds

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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.