PACAP suppresses dry eye signs by stimulating tear secretion

Abstract

Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

“…Nakamachi and coworkers [46] have recently described that PACAP eye drops stimulated tear secretion, increased cAMP release and aquaporin expression in the infraorbital lacrimal gland in mice and suppressed corneal keratinization in PACAP null animals. PACAP eye drops have also been shown to enhance corneal wound healing [47] and accelerate regeneration of corneal nerve endings [48].…”

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

“…39 Topical ocular application of PACAP has already been used to test local, corneal effects of the peptide. It has been found that PACAP, given in eye drops, enhances corneal wound recovery, 20,40,41 stimulates lacrimal secretion, 40,41 and accelerates nerve regeneration. 21 However, the effects of topical PACAP on the retina have never been investigated.…”

Pituitary adenylate cyclase‐activating polypeptide promotes eccrine gland sweat secretion

“…A recent study reported that PACAP and PAC1R mRNA are expressed in mouse skin, and that PAC1R immunoreactivity was observed in the basal, polygonal and granular layers of the epidermis . In addition, PACAP was reported to be localized in nerve fibres around exocrine tissue such as the mammary and lacrimal glands . Although PACAP is reported to be involved in inflammation of the skin, its effects on sweat production by eccrine glands have not been elucidated.…”

“…20 In addition, PACAP was reported to be localized in nerve fibres around exocrine tissue such as the mammary 21 and lacrimal glands. 22 Although PACAP is reported to be involved in inflammation of the skin, 20 its effects on sweat production by eccrine glands have not been elucidated. One study did report an observed ultracytochemical localization of adenylate cyclase after the stimulation of human sweat glands with PACAP.…”