PACAP suppresses dry eye signs by stimulating tear secretion

Area of Science:

• Ophthalmology
• Neuroendocrinology

Background:

• Dry eye syndrome is characterized by reduced tear volume or quality.
• Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a role in physiological processes.
• The involvement of PACAP in tear secretion and dry eye pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of PACAP in tear secretion and dry eye development.
• To evaluate the therapeutic potential of PACAP eye drops for dry eye disorder.

Main Methods:

• Utilized PACAP-null mice to model dry eye symptoms.
• Administered PACAP eye drops and assessed tear secretion, corneal keratinization, and lacrimal gland molecular changes.
• Investigated the involvement of PACAP receptor 1 (PAC1-R), cAMP, protein kinase A (PKA), and aquaporin 5 (AQP5).

Main Results:

• PACAP-null mice exhibited dry eye-like symptoms, including reduced tear secretion and corneal keratinization.
• PACAP eye drops significantly increased tear secretion and suppressed corneal keratinization in PACAP-null mice.
• PACAP treatment elevated cAMP and phosphorylated PKA levels in lacrimal glands, mediated via PAC1-R, and increased AQP5 membrane expression.

Conclusions:

• PACAP is crucial for maintaining normal tear secretion and ocular surface health.
• PACAP eye drops demonstrate therapeutic efficacy in a mouse model of dry eye.
• PACAP may represent a novel therapeutic agent for treating dry eye disorder.