Most living organisms on the earth have a circadian clock (internal clock) with about 24-hour period and adapt their important physiological functions to ambient light/dark cycles. In mammals, a master clock in the brain, the suprachiasmatic nucleus (SCN), gorverns body rhythms via hormonal and neural pathways. Disruption of circadian rhythms is known to be a risk factor for several kinds of diseases. In addition, it has been known that circadian clock is very important for the measurement of day length (photoperiod). Understanding the clever mechanisms of this clock regulation and photoperiodic time measurement will not only improve the productivity of animals, but also lead to the development of prevention or therapy for some diseases.
Mechanisms undelying glaucoma development and diurnal change of intraocular pressure
Glaucoma is the leading cause of blindness in Japan, and the number increases with age. It is estimated that more than 100 million people around the world will be affected by glaucoma by 2040, but effective prevention and cures have yet to be established. Understanding the mechanism of glaucoma will lead to the discovery of abnormal markers in the early stages of glaucoma, and is expected to lead to the development of new therapeutic agents.
１. Regulatory mechanisms of diurnal changes in intraocular pressure (IOP)
Eye stiffness (intraocular pressure; IOP), which causes glaucoma, is formed by the balance between aqueous humor production and drainage, and shows a circadian rhythm. Although nocturnal IOP increases in both diurnal and nocturnal animals, the detailed mechanism is unknown. In our previous research, we found that circadian changes in the sympathetic nerve noradrenaline (NE) and the stress hormone adrenocortical glucocorticoid (GC) produced IOP rhythms, but the detailed mechanism remains unclear. Therefore, we are aiming to understand the circadian regulatory mechanisms underlying aqueous humor production/drainage by NE and GC.
２.Glaucoma and lifestyles
As the aging of the population accelerates in developed countries, in order to maintain the quality of life as well as the national strength and labor force, it is necessary to keep our own health by improving lifestyles that do not rely on medical care as much as possible. Therefore, we aim to elucidate lifestyle habits such as sleep, diet, stress, and exercise related with IOP and glaucoma, using data science technology from human BIG data, and apply them to glaucoma prevention.
３. Glaucoma and nutrients
It has been suggested that certain diets and supplements may suppress the elevation of IOP and prevent glaucoma. However, the detail and the mechanism remains unclear. Therefore, we aim to identify nutrients and compounds that reduce IOP and prevent glaucoma by focusing on food nutrients using cells, mice, and humans BIG data, and to clarify the detailed mechanism. Improving eating habits can be expected to lead to an extension of healthy life expectancy.
Understanding of pineal physiological functions
Melatonin in the pineal gland, known as a sleep hormone, is secreted at night in both diurnal and nocturnal animals. Melatonin play an important role in seasonal time measurement in mammals. However, the effect on other physiological functions is not well understood. Furthermore, although pineal humoral factors other than melatonin are also synthesized, their physiological functions remain unknown. Therefore, we aim to elucidate the regulatory mechanisms of physiological functions of the pineal gland on circadian clock, neurodevelopment, behavior, emotion/mood, and sensory function, using melatonin-deficient and -proficient mouse strains.