TRPV4可以控制昼夜高血压和病态眼高血压
Sarah N Redmon1, Monika Lakk1, Yun-Ting Tseng1
1Department of Ophthalmology & Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
The Journal of physiology
|July 10, 2025
概括
在正常状态和疾病状态下,过渡性受体潜在化物异型4 (TRPV4) 通道对于眼睛高血压 (OHT) 至关重要. 通过控制眼内压力,抑制TRPV4显示出新的青光眼治疗方法的前景.
科学领域:
- 眼科医生 眼科 眼科
- 机械生物学 机械生物学
- 生理学 生理学 生理学
背景情况:
- 眼睛高血压 (OHT) 涉及机械应力和葡萄皮质类药物,影响传统的外流通道的透性和视力.
- 在健康人群中,生理夜间眼内压 (IOP) 的升高不会引起不良影响,与病理性OHT不同.
- 机械感应在调节生理与病理OHT中的作用及其对状网 (TM) 透性的影响仍然不清楚.
研究的目的:
- 研究机械感应,特别是短暂受体潜在化物异型4 (TRPV4) 在调节眼睛高血压 (OHT) 中的作用.
- 为了确定TRPV4的激活或抑制如何影响眼内压力 (IOP) 和轨道眼网格 (TM) 流出设施.
- 探索TRPV4作为一种潜在的治疗眼的目标.
主要方法:
- 使用了野生类型的小鼠和传统的外流特定的Trpv4淘汰模型.
- 用TRPV4激动剂 (GSK1016790A) 和抗剂 (HC-067047,GSK2193874) 进行局部和室内注射.
- 使用虹膜角膜角封闭,德甲治疗和聚烯微珠诱导的OHT.
- 评估了IOP,在3D纳米支架中进行外流设施,以及视网膜神经元保护.
主要成果:
- 对于由昼夜节律,角度阻塞和葡萄皮质类药物诱导的OHT,需要TRPV4激活.
- 当局部应用时,TRPV4激动剂降低了IOP,但在室内注射时提高了IOP.
- TRPV4抗剂在夜间OHT,德甲治疗和注射微珠的眼睛中降低了IOP.
- Trpv4 knockdown降低了闭眼和受保护的视网膜神经元中的内压.
- 在生物模拟TM模型中,TRPV4抑制增加了外流设施.
结论:
- TM驱动器中的Tonic TRPV4信号增加了外流阻力,导致OHT.
- 在模仿青光眼的生理和病理条件下,TRPV4对于维持OHT至关重要.
- 针对TRPV4呈现了一种新的治疗策略,用于控制青光眼中的IOP.
相关概念视频
Open Angle Glaucoma: Treatment
583
In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
Drugs such as carbonic anhydrase inhibitors, α2- and...
Drugs such as carbonic anhydrase inhibitors, α2- and...
583
Glaucoma: Overview
777
Glaucoma is an eye condition characterized by increased intraocular pressure that damages the retina and optic nerve, leading to irreversible blindness if left untreated. The human eye has various components, including the cornea, iris, pupil, lens, and optic nerve. Aqueous humor is secreted by the epithelium of the ciliary body in the posterior chamber and flows through the trabecular meshwork and canal of Schlemm, maintaining normal intraocular pressure. The trabecular meshwork and the canal...
777
Angle Closure Glaucoma: Treatment
702
Angle-closure glaucoma, or closed-angle glaucoma, is an eye condition where the iris bulges out and blocks the iridocorneal angle, resulting in a buildup of aqueous humor and increased intraocular pressure. Immediate medical attention is necessary due to the sudden onset of symptoms. The treatment for angle-closure glaucoma includes short-term and long-term approaches. Short-term treatment involves using eye drops like pilocarpine to lower intraocular pressure by increasing aqueous humor...
702
Hypertension II: Pathophysiology
90
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
90
Photoreceptors and Visual Pathways
6.5K
At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
6.5K
Neural Regulation of Blood Pressure
3.5K
The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
3.5K


