{"id":441,"date":"2023-08-01T17:47:50","date_gmt":"2023-08-01T08:47:50","guid":{"rendered":"https:\/\/www.agr.kyushu-u.ac.jp\/lab\/lrmb\/?page_id=441"},"modified":"2026-07-29T15:10:56","modified_gmt":"2026-07-29T06:10:56","slug":"research-contents-ikegami-group","status":"publish","type":"page","link":"https:\/\/www.agr.kyushu-u.ac.jp\/lab\/lrmb\/research-contents-ikegami-group\/","title":{"rendered":"Research contents -Ikegami group –"},"content":{"rendered":"

Research contents<\/h2>\n

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\u3000(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.<\/p>\n

Mechanisms undelying glaucoma development and diurnal change of intraocular pressure<\/h3>\n

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.<\/p>\n

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\uff11. Regulatory mechanisms of diurnal changes in intraocular pressure (IOP)<\/strong><\/p>\n

\u3000Eye stiffness (intraocular pressure; IOP), which causes glaucoma, is formed by the balance between aqueous humor production and drainage, and shows a circadian rhythm.<\/span><\/span> Although nocturnal IOP increases in both diurnal and nocturnal animals, the detailed mechanism is unknown.<\/span><\/span> 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.<\/span><\/span> Therefore, we are aiming to understand the circadian regulatory mechanisms underlying aqueous humor production\/drainage by NE and GC.\u00a0<\/span><\/span><\/span>More recently, we have elucidated how norepinephrine (NE), released from the superior cervical ganglion as sympathetic activity increases at night, acts on the aqueous humor outflow pathway to elevate nocturnal intraocular pressure. In the rapid response, NE suppresses the phagocytic activity of trabecular meshwork macrophages through the \u03b21-adrenergic receptor\u2013cAMP\u2013EPAC\u2013SHIP1 signaling pathway, thereby contributing to the nocturnal increase in intraocular pressure (Ikegami et al., <\/span>Communications Biology<\/span><\/em>, 2022). In the slower response, NE induces gene expression through the \u03b21-adrenergic receptor\u2013cAMP\u2013CREB\u2013RHOB pathway, providing a sustained mechanism for the regulation of intraocular pressure (Ikegami et al., <\/span>Communications Biology<\/span><\/em>, 2026).\u00a0<\/span>Furthermore, using mathematical modeling, we have clarified how intraocular pressure increases at night in both diurnal humans and nocturnal mice, despite their opposite activity phases.<\/span><\/p>\n

\uff12.Glaucoma and lifestyles<\/strong><\/p>\n

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.<\/span><\/span> 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.<\/span><\/span> <\/span><\/p>\n

\uff13. Glaucoma and nutrients<\/span><\/span><\/span><\/strong><\/p>\n

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.<\/p>\n

Macro-hormones: A new circulating molecular form created by endocrine\u2013immune interactions<\/h3>\n

Pituitary hormones have traditionally been considered to circulate primarily as free monomeric proteins. In contrast, high-molecular-weight complexes formed through the association of hormones with immunoglobulins or other serum components are known as \u201cmacro-hormones.\u201d These complexes have generally been regarded as rare pathological abnormalities that interfere with clinical hormone measurements.<\/p>\n

Our research has revealed that not only thyroid-stimulating hormone (TSH), but also luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL), frequently occur as high-molecular-weight complexes in the blood of rodents, livestock, and humans. We further found that these complexes are reduced in animals or serum lacking immunoglobulins and that immunoglobulin \u03ba light chains are components of the complexes. These findings suggest that macro-hormones may not simply be pathological sources of assay interference. Instead, they may represent a conserved physiological molecular state of circulating pituitary hormones in mammals. Association with immunoglobulins could provide a previously unrecognized mechanism for regulating hormone stability, circulating half-life, transport, storage, and the kinetics of receptor activation. We are currently investigating the molecular mechanisms underlying macro-hormone formation and how their abundance is regulated by physiological factors such as season, the reproductive cycle, and thyroid hormones. By elucidating this molecular system at the interface between the endocrine and immune systems, we aim to uncover a new principle of hormone regulation and contribute to more accurate interpretation of circulating hormone measurements in clinical settings.<\/p>\n

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