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 and Seiji Shioda ()
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Tomoya Nakamachi: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama
Hirokazu Ohtaki: Showa University School of Medicine
Tamotsu Seki: Showa University School of Medicine
Sachiko Yofu: Showa University School of Medicine
Nobuyuki Kagami: Showa University School of Medicine
Hitoshi Hashimoto: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
Norihito Shintani: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
Akemichi Baba: Hyogo University of Health Sciences
Laszlo Mark: Institute of Biochemistry and Medical Chemistry, Medical School, University of Pécs
Ingela Lanekoff: Uppsala University
Peter Kiss: MTA-PTE PACAP Lendulet Research Group, Centre for Neuroscience, University of Pécs
Jozsef Farkas: Showa University School of Medicine
Dora Reglodi: MTA-PTE PACAP Lendulet Research Group, Centre for Neuroscience, University of Pécs
Seiji Shioda: Innovative Drug Discovery, Global Research Center for Innovative Life Science, Hoshi University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12034

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