Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor

Toshihiro Imada,Shigeru Nakamura,Izumi Shibuya,Yusuke Izuta,Naoki Kitamura,Kenji F Tanaka,Ryuji Hisamura,Kazuo Tsubota,Kai Jin,Masataka Ito,Masaru Mimura

doi:10.1038/s41598-017-06022-4

Toshihiro Imada, Shigeru Nakamura + Show 9 more

Open Access

https://doi.org/10.1038/s41598-017-06022-4

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Abstract

Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion. We found that blood serotonin concentration, changed by feeding a diet deprived of the serotonin precursor tryptophan, correlated with tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy and autophagy. The combination of a decrease in serotonin with the interruption of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we found that the serotonin type 3a receptor expressed in LG acinar cells is involved in tear secretion via intracellular calcium mobilization. Our findings demonstrate that hormonal regulation by serotonin, in cooperation with the autonomic nervous system, regulates tear secretion.

Highlights

Physiological functions of peripheral organs are regulated by direct innervation by the central nervous system and a wide variety of hormones released from the different glands or tissues from which they are synthesized[1, 2]
We investigated the physiological role of blood 5-HT in tear secretion
Blood 5-HT concentration gradually decreased from day 1 after changing to a Trp-free diet, and was decreased by approximately 70% from day 7 compared with the initial value before changing diet (Fig. 1B, closed circles)

Summary

Introduction

Physiological functions of peripheral organs are regulated by direct innervation by the central nervous system and a wide variety of hormones released from the different glands or tissues from which they are synthesized[1, 2]. Aqueous tear fluid secretion from the lacrimal gland (LG) is necessary for ocular surface health and serves to maintain clear vision by creating a smooth, reflective surface and providing oxygen to the avascular corneal epithelium[11] Both the sympathetic and parasympathetic components of the autonomic nervous system innervate the LG, and the parasympathetic system plays an essential role in the regulation of LG tear secretory function[12]. Insufficient aqueous tear secretion leads to abnormalities in the ocular surface[11], ocular discomfort[18], and functional visual acuity[19], resulting in dry-eye syndrome[11] The etiology of this syndrome appears to be multifactorial[20], but little attention has been directed to the potential involvement of an imbalance between the autonomous nervous system and hormonal factors. We found that in addition to autonomic innervation, peripheral hormonal 5-HT plays a role in tear secretion, and that LG 5-HT3aR mediates these activities

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