Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama-shi, Toyama 930-8555, Japan.
Department of Anatomy, Showa University School of Medicine, Shinagawa-Ku, Tokyo 142-8555, Japan.
Nat Commun. 2016 Jun 27;7:12034. doi: 10.1038/ncomms12034.
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.
干眼症是由泪液体积或质量减少引起的。在这里，我们表明，垂体腺苷酸环化酶激活肽（PACAP）缺失小鼠会出现类似干眼症的症状，如角膜角化和泪液减少。PACAP 免疫反应与神经元标志物共定位，PACAP 受体（PAC1-R）免疫反应在小鼠眶下泪腺腺泡细胞中观察到。PACAP 眼药水可刺激泪液分泌，并增加眶下泪腺中的环磷酸腺苷（cAMP）和磷酸化（p）蛋白激酶 A 水平，这些水平可被 PAC1-R 拮抗剂或腺苷酸环化酶抑制剂预先处理所抑制。此外，这些眼药水可抑制 PACAP 缺失小鼠的角膜角化。PACAP 眼药水增加了眶下泪腺中膜上的水通道蛋白 5（AQP5）水平和 pAQP5 水平。眶下泪腺的 AQP5 siRNA 处理可减弱 PACAP 诱导的泪液分泌。基于这些结果，PACAP 可能在临床上可用于治疗干眼症。
