Nakamachi Tomoya
Faculty of Science, Graduate School of Science and Engineering, University of Toyama.
Nihon Yakurigaku Zasshi. 2018;151(6):232-238. doi: 10.1254/fpj.151.232.
Dry eye syndrome is defined as a disorder of the tear film caused by either a decreased production in tears or a disruption to the stability of the complex tear film, which causes damage to the ocular surface. It has been developed the medicine for dry eye syndrome focusing anti-inflammation or mucin secretion, however, no treatment has been developed focusing on the effect of elevation of the lacrimal secretion. We recently identified that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP receptor (PAC1-R) immunoreactivity was observed in the acinar cells of the mouse lacrimal gland. PACAP eye drop significantly stimulated tear secretion level, and the effect was suppressed by pretreatment with PAC1-R antagonist or adenylate cyclase inhibitor. PACAP eye drop on the PACAP KO mouse significantly increased the tear secretion, and continuous eye drop suppressed progression of the corneal keratinization. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane of acinar cells in lacrimal glands. AQP5 siRNA treatment significantly attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.
干眼综合征被定义为一种由泪液分泌减少或复杂泪膜稳定性破坏引起的泪膜紊乱，进而导致眼表损伤。针对干眼综合征，已经研发出了聚焦于抗炎或促进黏蛋白分泌的药物，然而，尚未研发出聚焦于提高泪液分泌效果的治疗方法。我们最近发现，垂体腺苷酸环化酶激活多肽（PACAP）基因敲除小鼠会出现类似干眼的症状，如角膜角质化和泪液减少。在小鼠泪腺的腺泡细胞中观察到了PACAP受体（PAC1-R）免疫反应性。PACAP滴眼液显著刺激泪液分泌水平，且该作用被PAC1-R拮抗剂或腺苷酸环化酶抑制剂预处理所抑制。给PACAP基因敲除小鼠滴注PACAP滴眼液可显著增加泪液分泌，持续滴注可抑制角膜角质化的进展。PACAP滴眼液可提高泪腺腺泡细胞膜上水通道蛋白5（AQP5）的水平。AQP5小干扰RNA处理可显著减弱PACAP诱导的泪液分泌。基于这些结果，PACAP在临床上可能对治疗干眼疾病有用。
