Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC

Huifeng Wang1, Zongzheng Zou2, Luqin Wan1

  • 1Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University Qingdao, China.

Insights

Periplocin, a natural compound, rejuvenates aged meibomian glands by boosting meibocyte renewal and lipid production. This treatment targets the SRC pathway, offering a potential therapy for age-related evaporative dry eye disease.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Pharmacology

Background:

  • Age-related meibomian gland dysfunction (MGD) is a primary cause of evaporative dry eye.
  • Reduced meibocyte renewal and lipid synthesis contribute to MGD in aging individuals.
  • Key markers like Ki67, ΔNp63, and Na+/K+ ATPase decline in aged meibomian glands.

Purpose of the Study:

  • To investigate the potential of periplocin, a Na+/K+ ATPase agonist, in treating age-related MGD.
  • To elucidate the mechanism of periplocin's action on meibocyte renewal and lipid synthesis.
  • To explore the role of the SRC pathway in periplocin's therapeutic effects.

Main Methods:

  • In vitro studies on meibocyte cell proliferation and stem cell activity.
  • In vivo studies using aged mice models.
  • Analysis of protein expression (Ki67, ΔNp63, Na+/K+ ATPase, SRC pathway markers).
  • Lipid accumulation assessment using LipidTox staining.
  • Pharmacological inhibition of the SRC pathway using saracatinib.

Main Results:

  • Periplocin promoted meibocyte proliferation and stem cell activity in vitro.
  • In aged mice, periplocin increased Na+/K+ ATPase, Ki67, and ΔNp63 expression, enhancing meibocyte renewal.
  • Periplocin treatment led to increased lipid accumulation in meibomian gland cells and tissues.
  • Aged meibomian glands showed inhibited SRC pathway activity, which periplocin reversed.
  • Inhibiting the SRC pathway blocked periplocin's positive effects on proliferation and lipid synthesis.

Conclusions:

  • Periplocin enhances meibocyte cell renewal and lipid synthesis in aged meibomian glands.
  • The therapeutic effects of periplocin are mediated through the SRC signaling pathway.
  • Periplocin shows promise as a therapeutic agent for age-related MGD.

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