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, L. Márk, Ingela Lanekoff, P. Kiss, Jozsef Farkas, D. Reglodi, Seiji Shioda

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Article number12034
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Jun 27 2016

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
secretions
polypeptides
Tears
Lacrimal Apparatus
Ophthalmic Solutions
glands
Aquaporin 5
mice
Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Dry Eye Syndromes
pituitary gland
Acinar Cells
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Small Interfering RNA
pretreatment
markers
inhibitors
Membranes

ASJC Scopus subject areas

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

Cite this

Nakamachi, T., Ohtaki, H., Seki, T., Yofu, S., Kagami, N., Hashimoto, H., ... Shioda, S. (2016). PACAP suppresses dry eye signs by stimulating tear secretion. Nature Communications, 7, [12034]. https://doi.org/10.1038/ncomms12034

PACAP suppresses dry eye signs by stimulating tear secretion. / Nakamachi, Tomoya; Ohtaki, Hirokazu; Seki, Tamotsu; Yofu, Sachiko; Kagami, Nobuyuki; Hashimoto, Hitoshi; Shintani, Norihito; Baba, Akemichi; Márk, L.; Lanekoff, Ingela; Kiss, P.; Farkas, Jozsef; Reglodi, D.; Shioda, Seiji.

In: Nature Communications, Vol. 7, 12034, 27.06.2016.

Research output: Contribution to journalArticle

Nakamachi, T, Ohtaki, H, Seki, T, Yofu, S, Kagami, N, Hashimoto, H, Shintani, N, Baba, A, Márk, L, Lanekoff, I, Kiss, P, Farkas, J, Reglodi, D & Shioda, S 2016, 'PACAP suppresses dry eye signs by stimulating tear secretion', Nature Communications, vol. 7, 12034. https://doi.org/10.1038/ncomms12034
Nakamachi T, Ohtaki H, Seki T, Yofu S, Kagami N, Hashimoto H et al. PACAP suppresses dry eye signs by stimulating tear secretion. Nature Communications. 2016 Jun 27;7. 12034. https://doi.org/10.1038/ncomms12034
Nakamachi, Tomoya ; Ohtaki, Hirokazu ; Seki, Tamotsu ; Yofu, Sachiko ; Kagami, Nobuyuki ; Hashimoto, Hitoshi ; Shintani, Norihito ; Baba, Akemichi ; Márk, L. ; Lanekoff, Ingela ; Kiss, P. ; Farkas, Jozsef ; Reglodi, D. ; Shioda, Seiji. / PACAP suppresses dry eye signs by stimulating tear secretion. In: Nature Communications. 2016 ; Vol. 7.
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