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感应受体 (CaSR) 调节眼睛表面的化物运输,其抑制促进眼睛表面的水分
Neel D Pasricha1, Ethan S Lindgren2, Rongshan Yan2
1Department of Ophthalmology, University of California, San Francisco, United States; Francis I. Proctor Foundation, University of California, San Francisco, United States.
The ocular surface
|June 13, 2024
概括
感应受体 (CaSR) 调节眼睛表面的离子运输. 抑制CaSR显著增加了眼分泌,这表明CaSR抑制剂可以治疗干眼疾病.
科学领域:
- 眼科医生 眼科 眼科
- 身体生理学 身体生理学
- 分子生物学分子生物学
背景情况:
- 眼睛表面的水分是对眼睛健康和预防干眼疾病至关重要的.
- 细胞外感应受体 (CaSR) 调节表皮细胞中的离子运输.
- 囊性纤维化转膜导电调节器 (CFTR) Cl-通道对于眼睛表面上皮质至关重要,但CaSR在此方面的作用尚未得到充分研究.
研究的目的:
- 研究CaSR在眼睛表面组织中的表达.
- 确定CaSR在调节眼睛表面离子运输和眼分泌中的功能作用.
主要方法:
- 通过对小鼠和人类的角膜和结膜进行免疫染来分析CaSR的表达.
- 在小鼠身上测量了眼皮表面电位差异和眼液体体积.
- 药物制剂,cinacalcet (CaSR激活剂) 和NPS-2143 (CaSR抑制剂),被局部应用.
主要成果:
- 在小鼠和人类的角膜和结膜上皮表达CaSR.
- 局部的CaSR激活剂抑制了福斯科林诱导的Cl-分泌和CFTR活性.
- 局部的CaSR抑制剂刺激了CFTR介导的Cl-分泌,并至少在8小时内增加了约60%的液体体积.
结论:
- 在眼睛表面,CaSR作为离子运输的关键调节器.
- 抑制CaSR可增强Cl和撕裂分泌,这表明其潜在的治疗应用.
- 目前正在临床开发中的CaSR抑制剂可能被重新用于治疗干眼疾病.
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