Evidence map›Paper›PMID 25481446›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2015

A thermo-responsive protein treatment for dry eyes.

Wan Wang, Aarti Jashnani, Suhaas R Aluri, Joshua A Gustafson, Pang-Yu Hsueh, Frances Yarber, Robert L McKown, Gordon W Laurie, Sarah F Hamm-Alvarez, J Andrew MacKay

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 47 citations in OpenAlex.

  1. Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Autophagy in the normal and diseased cornea.Experimental eye research · 2022
    Review
  7. Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.Advances in experimental medicine and biology · 2020
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. A novel elastin-like polypeptide drug carrier for cyclosporine A improves tear flow in a mouse model of Sjögren's syndrome.Journal of controlled release : official journal of the Controlled Release Society · 2018
    Article
  19. Article
  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

10 authors at 3 institutions in 1 country.

Wan WangDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Aarti JashnaniDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Suhaas R AluriDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Joshua A GustafsonDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Pang-Yu HsuehDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Frances YarberDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States.
Robert L McKownDepartment of Integrated Science and Technology, James Madison University, Harrisonburg, VA, United States.
Gordon W LaurieDepartment of Cell Biology, School of Medicine of the University of Virginia, Charlottesville, VA, United States.
Sarah F Hamm-AlvarezDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States; Department of Physiology and Biophysics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States.
J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United States; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States. Electronic address: jamackay@usc.edu.
University of Southern California · USJames Madison University · USUniversity of Virginia · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OOKHTENS, MURAD · 1995 to 2020
$21.8M
Research Supplements to Promote DiversityR01EY011386 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAMM-ALVAREZ, SARAH F · 1996 to 2025
$9.3M
Tear Protein Microbial RegulationR01EY026171 · NEI · UNIVERSITY OF VIRGINIA · PI LAURIE, GORDON WILLIAM · 2016 to 2025
$3.6M
Lacritin Regulated Ocular Surface HomeostasisR01EY024327 · NEI · UNIVERSITY OF VIRGINIA · PI LAURIE, GORDON WILLIAM · 2014 to 2017
$1.8M
A rapid, reversible switch for controlling intracellular traffickingR21EB012281 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACKAY, JOHN ANDREW · 2010 to 2011
$438k
NCI NIH HHS P30 CA014089NEI NIH HHS EY011386NEI NIH HHS R01 EY011386NEI NIH HHS R01 EY024327NEI NIH HHS R01 EY026171NIBIB NIH HHS R21 EB012281NIDDK NIH HHS P30 DK048522
6 · The paper itself

Abstract

Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin (Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium. Similar to other proteins placed on the ocular surface, the durability of its effect is limited by rapid tear turnover. Motivated by the rationale that a thermo-responsive coacervate containing Lacrt would have better retention upon administration, we have constructed and tested the activity of a thermo-responsive Lacrt fused to an elastin-like polypeptide (ELP). Inspired from the human tropoelastin protein, ELP protein polymers reversibly phase separate into viscous coacervates above a tunable transition temperature. This fusion construct exhibited the prosecretory function of native Lacrt as illustrated by its ability to stimulate β-hexosaminidase secretion from primary rabbit lacrimal gland acinar cells. It also increased tear secretion from non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis, when administered via intra-lacrimal injection. Lacrt ELP fusion proteins undergo temperature-mediated assembly to form a depot inside the lacrimal gland. We propose that these Lacrt ELP fusion proteins represent a potential therapy for dry eye disease and the strategy of ELP-mediated phase separation may have applicability to other diseases of the ocular surface.

Indexed as

ActinsAnimalsDacryocystitisDelayed-Action PreparationsDry Eye SyndromesElastinFemaleGlycoproteinsHexosaminidase BHot TemperatureHumansIn Vitro TechniquesLacrimal ApparatusMaleMice, Inbred C57BLMice, Inbred NODActinsDelayed-Action PreparationsElastinGlycoproteinsHexosaminidase BLACRT protein, humanProteinsRecombinant Fusion ProteinsElastin-like polypeptides (ELPs)Lacrimal glandLacritinProsecretoryThermo-responsiveUptake

Identifiers

PMID25481446
PMCPMC4456095
OpenAlexW1983006697

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.