Age-related decline of platelet-derived growth factor receptor alpha in mesenchyme surrounding meibomian gland leads to meibomian gland dysfunction

Ke Xiong

doi:10.1016/j.exer.2026.110986

Age-related decline of platelet-derived growth factor receptor alpha in mesenchyme surrounding meibomian gland leads to meibomian gland dysfunction

2026-05-23

0

PRE

AI

K

Ke Xiong

P

Peiyao Lin

Z

Zihan Wang

R

Ruimin Wu

T

Tangqin Mai

S

Shangzhang Tang

Y

Yue Chen

Y

Yuying Xiao

M

Min Fu

W

Wanjing Huang

G

Guijun Wu

Q

Qing Tan

S

Siyuan Zhu *

Y

Yaru Su *

DOI：10.1016/j.exer.2026.110986

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Abstract

En 中文

The meibomian glands (MGs) in the eyelids produce oil to prevent tear evaporation, a function that declines with age. The mechanisms underlying MGs homeostasis and the pathogenesis leading to age-related meibomian gland dysfunction (ARMGD) remain largely unexplored. MGs contain secretory acini enveloped by a substantial mesenchyme. Previous studies have identified that ARMGD resulted from the failure to replenish acinar cells due to their senescence. Few studies, however, explored the role of age-related changes in mesenchyme contributing to ARMGD. Here, we demonstrated that an age-dependent decline in platelet-derived growth factor receptor alpha (PDGFR-alpha) within the peri-glandular mesenchyme was associated with ARMGD progression in both mice and humans. Furthermore, we discovered PDGFR-alpha+ cells co-expressing hybrid mesenchymal-epithelial markers in mesenchyme adjacent to MGs. This led us to hypothesize the existence of a plastic cell population whose function was impaired by aging. In MGs of young mice, inhibiting PDGFR-alpha expression upregulated cellular senescence genes (p16INK4a and p21Cip1/Waf1) and downregulated epithelial marker gene (krt14) within the mesenchyme, indicating that PDGFR-alpha downregulation induced mesenchymal senescence and plasticity losing. Additionally, PDGFR-alpha inhibition in young mouse MGs reduced acinar cell count and proliferation (ki67 expression), culminating in MGs atrophy and evaporative dry eye. Our findings highlighted the significance of mesenchymal-epithelial interaction in maintaining MGs homeostasis and proposed PDGFR-alpha-signaling within mesenchyme as a potential therapeutic target for ARMGD.

Keywords:

Age

Meibomian gland dysfunction

Mesenchymal-epithelial interaction

Platelet-derived growth factor receptor alpha

Age-related decline of platelet-derived growth factor receptor alpha in mesenchyme surrounding meibomian gland leads to meibomian gland dysfunction

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