Promotion of tear secretion by pituitary adenylate cyclase-activating polypeptide (PACAP)

Article information
PACAP suppresses dry eye signs by stimulating tear secretion.
Nakamachi T, Ohtaki H, Seki T, Yofu S, Kagami N, Hashimoto H, Shintani N, Baba A, Mark L, Lanekoff I, Kiss P, Farkas J, Reglodi D, Shioda S.
Nat Commun. 2016 Jun 27;7:12034. PMID: 27345595

Overview
Dry eye is a common eye disease caused by a decrease in the amount of tears or a decline in the quality of tears.

Typical therapy consists of symptomatic treatment with artificial tears, but even if this approach provides temporary symptom relief, the prognosis is not always satisfactory.

In recent years, the authors had found that PACAP-deficient mice frequently suffer from corneal keratosis accompanied by tear depletion, but the function of PACAP and PACAP receptors in the lacrimal gland was not well understood.

Therefore, the authors investigated the action and mechanism of action of PACAP in tear secretion by lacrimal glands of PACAP-deficient mice.

Administration of eye drops containing PACAP to wild-type and PACAP-deficient mice resulted in increased tear secretion in both groups.

In addition, an increase in the protein level of the water channel protein aquaporin 5 (AQP5) was observed in the membrane fraction of lacrimal gland extract 30 minutes after the administration of PACAP.

Subsequently, when AQP5 siRNA was administered to the lacrimal gland using AteloGene, a marked decrease in the expression level of AQP5 and the amount of lacrimal secretion was observed, suggesting that PACAP promotes lacrimal secretion through AQP5.