Ryuji Hisamura
Keio University
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Publication
Featured researches published by Ryuji Hisamura.
PLOS ONE | 2010
Shigeru Nakamura; Shigeru Kinoshita; Norihiko Yokoi; Yoko Ogawa; Michiko Shibuya; Hideo Nakashima; Ryuji Hisamura; Toshihiro Imada; Tomohiro Imagawa; Masato Uehara; Izumi Shibuya; Murat Dogru; Samantha K. Ward; Kazuo Tsubota
Background Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study. Methodology/Principal Findings Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing. Conclusions/Significance These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers.
Aging Cell | 2018
Yusuke Izuta; Toshihiro Imada; Ryuji Hisamura; Erina Oonishi; Shigeru Nakamura; Emi Inagaki; Masataka Ito; Tomoyoshi Soga; Kazuo Tsubota
Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D‐3‐hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration. Metabolomic analysis showed that the antioxidant pentose phosphate pathway and its limiting enzyme, glucose‐6‐phosphate dehydrogenase (G6PD), were concomitantly preserved. Importantly, the upregulation of nuclear factor erythroid 2 p45‐related factor 2 (Nrf2), a regulator of G6PD, and elevation of the tricarboxylic acid cycles Nrf2 activator, fumarate, were also shared. Together, our findings suggest that CR provides retinal antioxidative defense by 3HB through the antioxidant Nrf2 pathway via modification of a tricarboxylic acid cycle intermediate during 3HB metabolism.
Scientific Reports | 2017
Toshihiro Imada; Shigeru Nakamura; Ryuji Hisamura; Yusuke Izuta; Kai Jin; Masataka Ito; Naoki Kitamura; Kenji F. Tanaka; Masaru Mimura; Izumi Shibuya; Kazuo Tsubota
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.
PLOS ONE | 2017
Sachiko Inoue; Motoko Kawashima; Ryuji Hisamura; Toshihiro Imada; Yusuke Izuta; Shigeru Nakamura; Masataka Ito; Kazuo Tsubota
Background Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye. Methods and Findings We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20–60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands. Conclusion Our results suggest that RJ improves tear volume in patients with dry eye. Trial Registration Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446)
Investigative Ophthalmology & Visual Science | 2007
Shigeru Nakamura; Michiko Shibuya; Hideo Nakashima; Ryuji Hisamura; Nozomi Masuda; Tomohiro Imagawa; Masato Uehara; Kazuo Tsubota
Nutrition & Metabolism | 2014
Shigeru Nakamura; Ryuji Hisamura; Sachiko Shimoda; Izumi Shibuya; Kazuo Tsubota
Investigative Ophthalmology & Visual Science | 2016
Imada Toshihiro; Shigeru Nakamura; Ryuji Hisamura; Yusuke Izuta; Yusuke Oshima; Tomomi Nemoto; Kazuo Tsubota
Investigative Ophthalmology & Visual Science | 2016
Kokoro Sano; Motoko Kawashima; Toshihiro Imada; Ryuji Hisamura; Shigeru Nakamura; Fumiya Izumiseki; Kenji F. Tanaka; Mitsuhiro Watanabe; Masaru Mimura; Kazuo Tsubota
Investigative Ophthalmology & Visual Science | 2015
Kokoro Sano; Motoko Kawashima; Akiko Ito; Imada Toshihiro; Ryuji Hisamura; Shigeru Nakamura; Mitsuhiro Watanabe; Kazuo Tsubota
Investigative Ophthalmology & Visual Science | 2015
Ryuji Hisamura; Shigeru Nakamura; Imada Toshihiro; Yusuke Izuta; Kazuo Tsubota