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PACAP suppresses dry eye signs by stimulating tear secretion

Author

Listed:
  • Tomoya Nakamachi

    (Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama
    Showa University School of Medicine)

  • 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
    iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University
    Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui)

  • 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
    Imaging Center for Life and Material Sciences, University of Pécs
    János Szentágothai Research Center, University of Pécs
    PTE-MTA Human Reproduction Research Group)

  • 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
    MTA-PTE PACAP Lendulet Research Group, Centre for Neuroscience, University of Pécs)

  • 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)

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.

Suggested Citation

  • Tomoya Nakamachi & Hirokazu Ohtaki & Tamotsu Seki & Sachiko Yofu & Nobuyuki Kagami & Hitoshi Hashimoto & Norihito Shintani & Akemichi Baba & Laszlo Mark & Ingela Lanekoff & Peter Kiss & Jozsef Farkas , 2016. "PACAP suppresses dry eye signs by stimulating tear secretion," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12034
    DOI: 10.1038/ncomms12034
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