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PACAP suppresses dry eye signs by stimulating tear secretion
Toyama Univ, Grad Sch Sci & Engn, Lab Regulatory Biol, 3190 Gofuku, Toyama, Toyama 9308555, Japan.;Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan..
Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan..
Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan..
Showa Univ, Sch Med, Dept Anat, Shinagawa Ku, Tokyo 1428555, Japan..
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2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 12034Article in journal (Refereed) Published
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Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 7, 12034
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Ophthalmology
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URN: urn:nbn:se:uu:diva-300076DOI: 10.1038/ncomms12034ISI: 000379110400001PubMedID: 27345595OAI: oai:DiVA.org:uu-300076DiVA: diva2:950735
Available from: 2016-08-02 Created: 2016-08-02 Last updated: 2017-11-28Bibliographically approved

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Lanekoff, Ingela

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