Evidence map›Paper›PMID 42171532›Full record

ArticleThe Journal of general physiology2026

Model of ocular surface ion and water transport predicts efficacy of dry eye therapeutics.

Varun Verma, Ethan S Lindgren, Marc H Levin, Onur Cil, Lukmanee Tradtrantip, Rongshan Yan, Neel D Pasricha, Alan S Verkman

Abstract read
In one paragraph

Article in The Journal of general physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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

8 authors.

Varun VermaUniversity of California, Berkeley , Berkeley, CA, USA.ORCID 0009-0008-4507-291X
Ethan S LindgrenDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.ORCID 0009-0003-2666-2432
Marc H LevinDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.ORCID 0009-0008-6004-5311
Onur CilDepartment of Pediatrics, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5178-0199
Lukmanee TradtrantipDepartments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, USA.ORCID 0009-0001-8414-5922
Rongshan YanDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-1505-1321
Neel D PasrichaDepartment of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2327-5221
Alan S VerkmanDepartments of Medicine and Physiology, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3713-2202

Funding

Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAKKARAJU, APARNA · 1985 to 2024
$16.8M
SLC26A3 (DRA) Inhibitors for Treatment of Hyperoxaluria and NephrolithiasisR01DK126070 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CIL, ONUR · 2020 to 2024
$1.6M
Roles of CaSR in ocular surface health and diseaseR01EY036139 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Onur Cil · 2024 to 2026
$1.2M
Human Ocular Surface ElectrophysiologyK08EY033859 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Neel Dave Pasricha · 2023 to 2026
$877k
All May See FoundationCystic Fibrosis FoundationNEI NIH HHS EY013574NEI NIH HHS EY033859NEI NIH HHS EY036139NEI NIH HHS K08 EY033859NEI NIH HHS P30EY002162NEI NIH HHS R01 EY036139NIDDK NIH HHS DK072517NIDDK NIH HHS DK126070NIDDK NIH HHS R01 DK126070Research to Prevent Blindness
6 · The paper itself

Abstract

The composition and volume of tear fluid lining the ocular surface are governed by the rates of lacrimal gland secretion, tear film evaporation, nasolacrimal drainage, and epithelial ion and water transport. Tear fluid hyperosmolality and reduced volume are key drivers of dry eye disease (DED) pathogenesis. We constructed a mathematical model to compute the composition and volume of tear fluid and epithelial cell compartments, with transport parameters specified for the mouse eye based on published data and in vivo measurements of ocular surface potential differences. The model accounted for transcellular and paracellular transport across the epithelia under open-circuit conditions utilizing flux equations for individual transport mechanisms, with mass balance constraints on solute and water content in cytoplasm and tear fluid. Model computations revealed a rough orthogonality between the determinants of tear fluid volume and osmolality in which lacrimal secretion and nasolacrimal drainage primarily regulate tear fluid volume, whereas evaporation and transepithelial osmosis primarily regulate tear fluid osmolality. Under DED conditions established by reduced lacrimal secretion and increased evaporation, the model predicted the efficacy of currently available DED therapies, including punctal plugs, humidification goggles, lacrimal gland stimulation, and artificial tear eye drops. The model also predicted the limited efficacy of anti-absorptive and pro-secretory drugs targeting epithelial ion transporters and the high efficacy of targeting epithelial water permeability or paracellular ion permeability. The modeling herein provided quantitative predictions to prioritize drug targets for DED to drive the development of novel therapies.

Indexed as

Dry Eye SyndromesModels, BiologicalTearsWaterAnimalsBiological TransportHumansIon TransportLacrimal ApparatusMiceOphthalmic SolutionsOsmolar ConcentrationOphthalmic SolutionsWater

Identifiers

PMID42171532
PMCPMC13335528

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.