Evidence map›Paper›PMID 39414024›Full record

ArticleThe ocular surface2024

Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease.

Erin A Hisey, Sydni Wong, Sangwan Park, Kevin Aguirre Gamarra, Sara A Adelman, Kelly E Knickelbein, Melinda Quan, Michelle H Ferneding, Michelle McCorkell, Nicole Daley and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The ocular surface, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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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

25 authors.

Erin A HiseyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Sydni WongDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Sangwan ParkDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Kevin Aguirre GamarraDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Sara A AdelmanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Kelly E KnickelbeinDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA; Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Melinda QuanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Michelle H FernedingDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Michelle McCorkellDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Nicole DaleyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Vanessa UrenoDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Sophie LeDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Monica ArdonDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Liana WilliamsDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Bryan PuentesDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Morgan BowmanDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Monica J MottaDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
Hoang Quoc Hai PhamDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Amber WilkersonDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Seher YukselDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
James V JesterDepartment of Ophthalmology and Biomedical Engineering, University of California-Irvine, Irvine, CA, 92697, USA.
Sara M ThomasyDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA; Department of Ophthalmology and Vision Science, School of Medicine, University of California-Davis, Davis, CA, 95616, USA.
Joshua T MorganDepartment of Bioengineering, University of California-Riverside, Riverside, CA, 92521, USA.
Igor A ButovichDepartment of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Brian C LeonardDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA; Department of Ophthalmology and Vision Science, School of Medicine, University of California-Davis, Davis, CA, 95616, USA. Electronic address: bcleonard@ucdavis.edu.

Funding

VISION RESEARCH CORE GRANTP30EY012576 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI W MARTIN USREY · 1999 to 2026
$18.9M
Modulation of Signal Transduction by Nano-TopographyR01EY016134 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, CHRISTOPHER JOHN, THOMASY, SARA MICHELLE · 2006 to 2023
$5.1M
Vision Science Training Program: Cornea to CortexT32EY015387 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI MARIE E BURNS · 2003 to 2026
$4.8M
Age-Related Meibomian Gland DysfunctionR01EY021510 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI James V Jester · 2011 to 2026
$4.8M
Meibogenesis in Health, Disease, and Aging - Administrative SupplementR01EY027349 · NEI · UT SOUTHWESTERN MEDICAL CENTER · PI BUTOVICH, IGOR A · 2017 to 2025
$2.9M
UC Davis DVM/PhD Medical Scientist Training ProgramT32GM136559 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Xinbin Chen, Bethany Paige Cummings · 2020 to 2026
$2.2M
Students Training in Advanced Research (STAR) ProgramT35OD010956 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DANIKA L BANNASCH · 2012 to 2026
$1.6M
Modulation of Hsp90 signaling to limit corneal fibrosis and improve ocular drug penetrationK08EY028199 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD, BRIAN C. · 2017 to 2021
$1.1M
Redefining the factors that determine tear film stability to develop novel therapeutics for evaporative dry eye diseaseF30EY035132 · NEI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Erin Alissa Hisey · 2023 to 2026
$192k
NEI NIH HHS F30 EY035132NEI NIH HHS K08 EY028199NEI NIH HHS P30 EY012576NEI NIH HHS R01 EY016134NEI NIH HHS R01 EY021510NEI NIH HHS R01 EY027349NEI NIH HHS T32 EY015387NIGMS NIH HHS T32 GM136559NIH HHS T35 OD010956
6 · The paper itself

Abstract

purposeThere is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints.

methodsWildtype and Awat2 KO mice between 1 and 18 months of age were used. Ocular examinations and advanced imaging were performed. The lipidomic composition and in situ melting temperature of meibum were determined. qPCR was performed to define ocular surface gene and pro-inflammatory transcript expression. Dynamic contact angle goniometry was performed to assess the adherence capability of the ocular surface.

resultsAwat2 KO mice have mild, white, hyperreflective corneal opacities of the anterior stroma and significantly enlarged apical epithelial cells (P = 0.0004). In Awat2 KO meibum, wax esters were 9-10 times lower than in wildtype meibum. Additionally, meibum melting temperature increased from 32° to 47 °C (P < 0.0001), leading to impaired meibum secretion and dilation of the central duct. Awat2 KO corneal epithelia had significantly decreased mucin expression (Muc1 and Muc4, P = 0.0043) and increased interferon-γ production (P = 0.0303). Awat2 KO globes have a significantly shortened time of droplet adherence to their ocular surface (P = 0.0053), indicating a decreased tear film adherence capacity. Wildtype corneal epithelia does not express Awat2, indicating that the EDED phenotype is secondary to the loss of Awat2 from the meibomian glands.

conclusionsAwat2 KO mice recapitulate many of features of human MGD and EDED, representing a model to test novel therapeutics.

Indexed as

Disease Models, AnimalDry Eye SyndromesMeibomian Gland DysfunctionMeibomian GlandsMice, KnockoutTearsAcyltransferasesAnimalsFemaleLipid MetabolismMiceMice, Inbred C57BLAcyltransferasesDynamic contact angle goniometryEvaporative dry eye diseaseHeat stage cross-polarized light microscopyIn vivo confocal microscopyMeibomian gland dysfunctionMeibomian gland inspissationMouse models of dry eye diseaseOptical coherence tomography

Identifiers

PMID39414024
PMCPMC11879417

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Registered trials

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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.