Cytarabine chemotherapy induces meibomian gland dysfunction

Area of Science:

• Ophthalmology
• Oncology
• Cell Biology

Background:

• Cytarabine (Ara-C) chemotherapy is known to cause side effects that mimic meibomian gland dysfunction (MGD).
• The precise pathological mechanisms linking Ara-C to MGD remain incompletely understood.
• Investigating these mechanisms is crucial for developing supportive therapies for cancer patients experiencing ocular side effects.

Purpose of the Study:

• To investigate the pathological effects of Cytarabine (Ara-C) on meibomian glands (MGs) and ocular surface in a rodent model.
• To explore the role of PPARγ signaling in Ara-C-induced MGD.
• To evaluate the therapeutic potential of rosiglitazone in mitigating Ara-C-induced MGD.

Main Methods:

• Mice were treated with Ara-C, with or without rosiglitazone (a PPARγ agonist), for seven days.
• Ocular surface examinations were performed using slit-lamp biomicroscopy.
• Immunofluorescence, Oil Red O staining, and Western blotting were employed to assess MG pathology, lipid metabolism, proliferation, and protein expression.

Main Results:

• Ara-C induced ocular surface damage, including corneal defects, MG orifice plugging, acinar dropout, and lacrimal gland dysfunction.
• Ara-C inhibited MG progenitor cell proliferation and differentiation, leading to ductal hyperkeratinization and lipid metabolism disruption via PPARγ downregulation.
• Rosiglitazone treatment ameliorated Ara-C-induced MGD, restored LG function, improved MG lipid metabolism, and reduced oxidative stress.

Conclusions:

• Systemic Ara-C chemotherapy exerts direct cytotoxic effects on the ocular surface, leading to MGD.
• PPARγ signaling plays a critical role in the pathogenesis of Ara-C-induced MGD.
• Restoration of PPARγ activity with rosiglitazone effectively mitigates the pathological alterations associated with Ara-C-induced MGD.