Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice.
Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice.
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DOI：
10.1038/s42003-022-03295-y
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发表时间：
2022-04-08
影响因子：
5.9
通讯作者：
Masubuchi S
中科院分区：
文献类型：
--
作者：
Ikegami K;Masubuchi S
眼内压（IOP）是青光眼发展的重要因素，其涉及房水（AH）动力学，具有来自睫状体的流入和通过小梁网（TM）的流出。IOP具有由交感去甲肾上腺素（NE）或肾上腺糖皮质激素（GC）引起的昼夜节律。在此，我们研究了GC/NE在AH流出中的参与。小鼠流入/流出的药理学预防表明昼夜流出增加，这与TM吞噬作用有关。NE对永生化人TM细胞的吞噬功能有非自维持性抑制作用，而GC则无此作用。药理学和反向遗传学方法鉴定了β1-肾上腺素能受体（AR）介导的交换蛋白，这些蛋白直接被环磷酸腺苷（EPAC）-SHIP 1信号激活激活，通过消融磷脂酰肌醇三磷酸，调节吞噬杯形成。此外，我们揭示了吞噬作用参与β1-AR-EPAC-SHIP 1介导的小鼠夜间IOP升高。提示NE抑制TM的吞噬作用可通过AH流出调节眼压节律。这一发现可能有助于青光眼管理。发现可引起青光眼的眼内压受夜间交感去甲肾上腺素的影响，其通过β1-肾上腺素能受体介导的cAMP-EPAC-SHIP 1激活抑制小梁网细胞中的吞噬作用。
Intraocular pressure (IOP) is an important factor in glaucoma development, which involves aqueous humor (AH) dynamics, with inflow from the ciliary body and outflow through the trabecular meshwork (TM). IOP has a circadian rhythm entrained by sympathetic noradrenaline (NE) or adrenal glucocorticoids (GCs). Herein, we investigated the involvement of GC/NE in AH outflow. Pharmacological prevention of inflow/outflow in mice indicated a diurnal outflow increase, which was related to TM phagocytosis. NE showed a non-self-sustained inhibition in phagocytosis of immortalized human TM cells, but not GC. The pharmacological and reverse genetic approaches identified β1-adrenergic receptor (AR)-mediated exchange proteins directly activated by cyclic adenosine monophosphate (EPAC)-SHIP1 signal activation by ablation of phosphatidylinositol triphosphate, regulating phagocytic cup formation. Furthermore, we revealed the phagocytosis involvement in the β1-AR-EPAC-SHIP1-mediated nocturnal IOP rise in mice. These suggest that TM phagocytosis suppression by NE can regulate IOP rhythm through AH outflow. This discovery may aid glaucoma management. Intraocular pressure, which can cause glaucoma, is found to be affected by nocturnal sympathetic noradrenaline, which inhibits phagocytosis in trabecular meshwork cells through β1-aderenergic receptor mediated cAMP-EPAC-SHIP1 activation.
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影响因子：
3.9
作者：
El-Shabrawi, Y;Eckhardt, M;Ardjomand, N
通讯作者：
Ardjomand, N
健康受试者、原发性开角型青光眼和正常张力型青光眼患者的昼夜眼压模式与隐形眼镜传感器
影响因子：
3.4
作者：
Agnifili, Luca;Mastropasqua, Rodolfo;Mastropasqua, Leonardo
通讯作者：
Mastropasqua, Leonardo
影响因子：
8.1
作者：
Borrás T;Buie LK;Spiga MG;Carabana J
通讯作者：
Carabana J
影响因子：
4.4
作者：
Jain, Ankur;Liu, Xiangyang;Clark, Abbot F.
通讯作者：
Clark, Abbot F.
影响因子：
4.4
作者：
Ikegami, Keisuke;Shigeyoshi, Yasufumi;Masubuchi, Satoru
通讯作者：
Masubuchi, Satoru