PACAP suppresses dry eye signs by stimulating tear secretion

Tomoya Nakamachi, Hirokazu Ohtaki, Tamotsu Seki, Sachiko Yofu, Nobuyuki Kagami, Hitoshi Hashimoto, Norihito Shintani, Akemichi Baba, Laszlo Mark, Ingela Lanekoff, Peter Kiss, Jozsef Farkas, Dora Reglodi, Seiji Shioda

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42 Citations (Scopus)


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.

Original languageEnglish
Article number12034
JournalNature communications
Publication statusPublished - Jun 27 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    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. (2016). PACAP suppresses dry eye signs by stimulating tear secretion. Nature communications, 7, [12034].