Piezo 1 is involved in intraocular pressure regulation

Morozumi, Wataru; Aoshima, Kota; Inagaki, Satoshi; Iwata, Yuji; Nakamura, Shinsuke; Hara, Hideaki; Shimazawa, Masamitsu

doi:10.1016/j.jphs.2021.06.005

Cited by 22 publications

(11 citation statements)

References 41 publications

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“…This implies it may be involved in the regulation of ICP. Studies have also indicated a role for Piezo1 in the regulation of intraocular pressure ( 38 ). In addition, force exerted by unidirectional laminar flow activates Piezo1-mediated mechanotransduction signaling in lymphatic vessels to control sprouting, expansion, and long-term maintenance ( 7 ).…”

Section: Resultsmentioning

confidence: 99%

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

Matrongolo,

Ang,

et al. 2023

Journal of Clinical Investigation

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Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associate with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in Twist1 +/– :5xFAD transgenic Alzheimer’s disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show that Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest that CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.

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Section: Resultsmentioning

confidence: 99%

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

Matrongolo,

Ang,

et al. 2023

Journal of Clinical Investigation

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“…Spheroid release requires a loss of cell-cell and cell-ECM interactions between the spheroid and the substrate/monolayer. As Piezo1 activity has been shown to induce expression of matrix metalloproteinases (MMPs) ( 32 , 33 ), we evaluated whether MMP activity affected stiffness-induced collective detachment. Batimastat, a pan-MMP inhibitor, was incorporated into the model and found to negate the stiffness-induced increase in collective detachment (Fig.…”

Section: Resultsmentioning

confidence: 99%

The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment

Micek,

Yang,

Dutta

et al. 2024

Sci. Adv.

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Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified PIEZO1 −/− OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.

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“…Piezo1, a mechanosensitive ion channel expressed in vascular endothelial cells and smooth muscle, is suggested to control cerebral capillary blood flow, vascular tone, and blood pressure (36, 37), implying it may be involved in the regulation of ICP. Recent studies have also indicated a role for Piezo1 in the regulation of intraocular pressure (38). In addition, force exerted by unidirectional laminar flow activates Piezo1-mediated mechanotransduction signaling in lymphatic vessels to control sprouting, expansion, and long-term maintenance of lymphatic networks (7).…”

Section: Resultsmentioning

confidence: 99%

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

Matrongolo,

Ang,

et al. 2023

Preprint

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Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associates with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup inTwist1+/−:5xFADtransgenic Alzheimer’s disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.

show abstract

Piezo 1 is involved in intraocular pressure regulation

Cited by 22 publications

References 41 publications

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment

Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice

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