2023 Fiscal Year Final Research Report
The role of endogenous melatonin in the diurnal variation of intraocular pressure
| Project/Area Number |
21K09739
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56060:Ophthalmology-related
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | メラトニン / Annat / Hiomt / マウス / 眼圧 / 松果体 / 網膜 |
|---|
| Outline of Final Research Achievements |
This study aimed to elucidate the role of the melatonin system in the diurnal variation of intraocular pressure, from both clinical and basic perspectives. We investigated the circadian variation in 24-hour intraocular pressure in patients with untreated primary open-angle glaucoma using a contact lens sensor (CLS) and examined its association with genetic polymorphisms in various genes including melatonin-related genes.There was a significant association between the rs3760138 gene polymorphism of AANAT, one of the enzymes responsible for melatonin synthesis, and the acrophase of CLS measurements. By crossing both B6J.MSM-Aanat and B6J.MSM-Hiomt mice, congenic mice with endogenous melatonin production (Aanat(+/+);Hiomt(+/+)) and without melatonin production (Aanat( -/-);Hiomt(-/-)) were created. As a result of measuring 24-hour intraocular pressure fluctuations in both mice, endogenous melatonin production reduces the intraocular pressure variation between the light and dark periods.
|
| Free Research Field |
眼科学
|
| Academic Significance and Societal Importance of the Research Achievements |
メラトニン合成酵素の1つであるAANATの遺伝子多型と眼圧日内変動との関連を初めて明らかにした。概日リズムの出力系であるメラトニン産生が眼圧日内変動の関連因子の一つである可能性が示唆された。実験動物用マウスの多くはメラトニン合成能が欠如しているため、眼圧日内変動に対する内因性メラトニンの影響は不明であった。本研究によって内因性メラトニン産生の有無の影響についてコンジェニックなマウスでの検討が可能となった。内因性メラトニン産生は眼圧日内変動を抑えることが初めて明らかとなった。今後、内因性メラトニンの緑内障に対する影響やメラトニンおよび関連物質の緑内障治療薬としての可能性の解明が期待される。
|
