The effects of age and dysfunction on meibomian gland population dynamics.

Wiedemann, Julie; Kashgari, Ghaidaa; Lane, Shelley; Leonard, Brian C; Knickelbein, Kelly E; Andersen, Bogi; Jester, James V

Wiedemann, Julie; Kashgari, Ghaidaa; Lane, Shelley; Leonard, Brian C; Knickelbein, Kelly E; Andersen, Bogi; Jester, James V.

Afiliação

Wiedemann J; Mathematical, Computational and Systems Biology (MCSB) Program, University of California, Irvine, Irvine, CA, USA.
Kashgari G; Department of Biological Chemistry and Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Lane S; Department of Ophthalmology and Biomedical Engineering, University of California, Irvine, Irvine, CA, USA.
Leonard BC; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA; Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, Davis, CA, USA.
Knickelbein KE; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
Andersen B; Mathematical, Computational and Systems Biology (MCSB) Program, University of California, Irvine, Irvine, CA, USA; Department of Biological Chemistry and Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA. Electronic address: bogi@uci.edu.
Jester JV; Department of Ophthalmology and Biomedical Engineering, University of California, Irvine, Irvine, CA, USA. Electronic address: jjester@uci.edu.

Ocul Surf ; 34: 194-209, 2024 Aug 08.

Article em En | MEDLINE | ID: mdl-39122180

ABSTRACT

ABSTRACT

PURPOSE:

While meibomian gland dysfunction (MGD) is widely recognized as a major cause of evaporative dry eye disease, little is known about normal gland differentiation and lipid synthesis or the mechanism underlying gland atrophy and abnormal lipid secretion. The purpose of this study was to use single-cell and spatial transcriptomics to probe changes in cell composition, differentiation, and gene expression associated with two murine models of MGD age-related gland atrophy in wild-type mice and altered meibum quality in acyl-CoA wax alcohol acyltransferase 2 (Awat2) knockout (KO) mice.

METHODS:

Young (6 month) and old (22 month) wild type, C57Bl/6 mice and young (3 month) and old (13 month) Awat2 KO mice were used in these studies. For single-cell analysis, the tarsal plate was dissected from the upper and lower eyelids, and single cells isolated and submitted to the UCI Genomic Core, while for the spatial analysis frozen tissue sections were shipped to Resolve Biosciences on dry ice and sections probed in duplicate using a meibomian gland specific, 100 gene Molecular Chartography panel.

RESULTS:

Analysis of gene expression patterns identified the stratified expression of lipogenic genes during meibocyte differentiation, which may control the progressive synthesis of meibum lipids; an age-related decrease in meibocytes; and increased immune cell infiltration. Additionally, we detected unique immune cell populations in the Awat2 KO mouse suggesting activation of psoriasis-like, inflammatory pathways perhaps caused by ductal dilation and hyperplasia.