Oral Administration of Royal Jelly Restores Tear Secretion Capacity in Rat Blink-Suppressed Dry Eye Model by Modulating Lacrimal Gland Function Toshihiro Imada 1 , Shigeru Nakamura 1 *, Naoki Kitamura 2 , Izumi Shibuya 2 , Kazuo Tsubota 1 1 Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan, 2 Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, Tottori, Japan Abstract Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG. Citation: Imada T, Nakamura S, Kitamura N, Shibuya I, Tsubota K (2014) Oral Administration of Royal Jelly Restores Tear Secretion Capacity in Rat Blink- Suppressed Dry Eye Model by Modulating Lacrimal Gland Function. PLoS ONE 9(9): e106338. doi:10.1371/journal.pone.0106338 Editor: Michele Madigan, Save Sight Institute, Australia Received March 27, 2014; Accepted June 24, 2014; Published September 22, 2014 Copyright: ß 2014 Imada et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by a Yamada research grant from Yamada Bee company, Inc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. This funding source had no involvement in the study design, data collection and analysis decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: vdtwork@gmail.com Introduction The ocular surface, comprising the cornea and conjunctiva, is covered by a thin layer of an aqueous tear film secreted from the lacrimal gland (LG). The role of tear fluid is to provide a proper environment to maintain homeostasis for the ocular surface [1]. The tear film acts as the first defense system against environmental microbes, desiccation, and foreign bodies and also smooths the refractive surface of the transparent cornea [2]. Dry eye disease is a multifactorial disorder characterized by the status of the tear film, results in ocular discomfort and visual impairment [3], and has become a major public health issue in industrial societies that have many of the risk factors for this disease, including the use of digital devices (computers, tablets, and smart phones) [4]. The incidence of dry eye was previously showed to be particularly high in workers that stare at the screens of technological devices [5,6]. We previously demonstrated that a chronic reduction in tear production was induced by extended computer use in both human and animal studies, and suggested that LG hypofunction may be a critical mechanism in digital device-induced dry eye [7]. The function of the LG also has been shown to decrease with aging, a known potent risk factor for dry eye [8,9]. Therefore, the discovery and development of novel preventative interventions that could maintain healthy LG function may have considerable clinical implications. However, temporal tear replacement therapy, the frequent application of artificial tear eye drops, has long been used in the basis management of dry eye [10]. Beekeeping products have been deeply rooted in the lives of different people and cultures worldwide for thousands of years as a nutritional source and medicine. The main products of beekeeping are honey, royal jelly, propolis, pollen, and bee larva produced or collected by Apidae. These products exhibit a wide range of biological effects, including antibacterial [11,12], antiviral [13], anti-inflammatory [14,15], and/or antiallergenic actions [16,17]. Honey eye drops have been used in corneal wound therapy as a traditional medicine [18] in the ophthalmic field and propolis was shown to protect against neuronal damage in the retina [19]. However little is known about the effects of honey bee products on tear secretion capacity in dry eye. In the present study, we assessed the potential usefulness of orally applied honey bee products as a preventative intervention in dry eye associated with the excessive use of digital devices. We used a blink-suppressed dry eye model: persistent strain by swing treatment in combination with exposure to an evaporative environment, which induces disordered tear dynamics, decreased blink frequency, and LG dysfunction. This dry eye model was established based on the concept that the long-lasting use of technological devices is associated with a marked reduction in the frequency of blinking while gazing at the screen and awkward postures in a dry environment [7]. PLOS ONE | www.plosone.org 1 September 2014 | Volume 9 | Issue 9 | e106338