期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/ncomms12034
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资金
- JSPS KAKENHI Grant [24592680, 24592681, 23249079, 15K15670, 26293020, 26670122, 16H02684, 15H01288]
- JSPS Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers [S2603]
- Hungarian Scientific Research Fund (OTKA) [K104984]
- Lendulet Program
- Arimura Foundation [KTIA_NAP_13-1-2013-0001]
- Grants-in-Aid for Scientific Research [26293020, 15K15670, 24592680, 23249079, 15H01288, 26670122, 24592681, 16H02684] Funding Source: KAKEN
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.
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