Methods and compositions for fluid drainage by Piezo ion channel activation
A method of treating impaired lymphatic function in a subject is provided. The method includes a step of inducing activation of Piezo1 ion channels in lymphatic tissues of a subject having impaired lymphatic function. Similarly, a method of treating ocular hypertension or glaucoma in a subject includes a step of inducing activation of Piezo1 ion channels in an eye of a subject having an ocular pressure that is greater than 22 mm Hg. Finally, a method of treating ocular hypertension or glaucoma in a subject includes a step of inducing activation of Piezo1 ion channels in an eye of a subject having an ocular pressure that is greater than 22 mm Hg.
1. A method of treating impaired lymphatic function in a subject, the method comprising the step of:
administering a pharmaceutical composition to the subject having dysfunctional lymphatic valves in lymphatic tissues to treat the dysfunctional lymphatic valves in the lymphatic tissues, wherein the pharmaceutical composition includes a Piezo1 agonist that is 2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-thiadiazole, wherein administration of the pharmaceutical composition is in a sufficient amount to enhance expression of lymphatic valve-associated genes FOXC2, GATA2, CX37, and LAMA5 through Piezo1-dependent pathways, and to promote expression of ITGA9 through Piezo1-independent pathways, thereby promoting formation and function of lymphatic valves.
2. The method of claim 1 further comprising applying oscillatory shear stress to the lymphatic tissues.
3. The method of claim 2 , wherein the oscillatory shear stress does not activate Piezo2 ion channels in the lymphatic tissues.
4. The method of claim 2 , wherein the applying step includes directing ultrasound pulses towards the lymphatic tissues.
5. The method of claim 4 , wherein the ultrasound pulses have a frequency of 43 megahertz (MHz).
6. A method of treating ocular hypertension or glaucoma in a subject, the method comprising the step of:
administering a pharmaceutical composition to the subject having an ocular pressure that is greater than 22 mm Hg, wherein the pharmaceutical composition includes a Piezo1 agonist that is 2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-thiadiazole, wherein the subject has ocular hypertension or glaucoma, wherein administration of the pharmaceutical composition is in a sufficient amount to enhance expression of lymphatic valve-associated genes FOXC2, GATA2, CX37, and LAMA5 through Piezo1-dependent pathways, and to promote expression of ITGA9 through Piezo1-independent pathways.
7. The method of claim 6 further comprising applying oscillatory shear stress to the eye.
8. The method of claim 7 , wherein the oscillatory shear stress does not activate Piezo2 ion channels in the eye.
9. The method of claim 7 , wherein the applying step includes directing ultrasound pulses towards the eye.
10. The method of claim 9 , wherein the ultrasound pulses have a frequency of 43 megahertz (MHz).
11. The method of claim 7 , wherein the pharmaceutical composition is administered in an amount effective for reducing the ocular pressure.
12. The method of claim 6 , wherein the subject has glaucoma.