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The Piezo1 ion channel in glaucoma: a new perspective on mechanical stress

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Abstract

Glaucomatous optic nerve damage caused by pathological intraocular pressure elevation is irreversible, and its course is often difficult to control. This group of eye diseases is closely related to biomechanics, and the correlation between glaucoma pathogenesis and mechanical stimulation has been studied in recent decades. The nonselective cation channel Piezo1, the most important known mechanical stress sensor, is a transmembrane protein widely expressed in various cell types. Piezo1 has been detected throughout the eye, and the close relationship between Piezo1 and glaucoma is being confirmed. Pathological changes in glaucoma occur in both the anterior and posterior segments of the eye, and it is of great interest for researchers to determine whether Piezo1 plays a role in these changes and how it functions. The elucidation of the mechanisms of Piezo1 action in nonocular tissues and the reported roles of similar mechanically activated ion channels in glaucoma will provide an appropriate basis for further investigation. From a new perspective, this review provides a detailed description of the current progress in elucidating the role of Piezo1 in glaucoma, including relevant questions and assumptions, the remaining challenging research directions and mechanism-related therapeutic potential.

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References

  1. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268–79.

    Article  PubMed  Google Scholar 

  2. Anderson DR, Drance SM, Schulzer M. Collaborative normal-tension glaucoma study G. Natural history of normal-tension glaucoma. Ophthalmology. 2001;108(2):247–53.

    Article  CAS  PubMed  Google Scholar 

  3. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429–40.

  4. Noecker RJ. The management of glaucoma and intraocular hypertension: current approaches and recent advances. Ther Clin Risk Manag. 2006;2(2):193–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Grant WM. Further studies on facility of flow through the trabecular meshwork. A.M.A. Arch Ophthalmol. 1958;60(4 Part 1), 523–533.

  6. Corey DP, Hudspeth AJ. Response latency of vertebrate hair cells. Biophys J. 1979;26(3):499–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330(6000):55–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nagase T, Seki N, Ishikawa K, et al. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 1996;3(5):321–9.

    Article  CAS  PubMed  Google Scholar 

  9. Satoh K, Hata M, Takahara S, et al. A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes. Brain Res. 2006;1108(1):19–27.

    Article  CAS  PubMed  Google Scholar 

  10. Coste B, **ao B, Santos JS, et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature. 2012;483(7388):176–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ge J, Li W, Zhao Q, et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015;527(7576):64–9.

    Article  CAS  PubMed  Google Scholar 

  12. Woo SH, Ranade S, Weyer AD, et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature. 2014;509(7502):622–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Woo SH, Lukacs V, de Nooij JC, et al. Piezo2 is the principal mechanotransduction channel for proprioception. Nat Neurosci. 2015;18(12):1756–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu J, Lewis AH, Grandl J. Touch, tension, and transduction—the function and regulation of Piezo Ion channels. Trends Biochem Sci. 2017;42(1):57–71.

    Article  PubMed  CAS  Google Scholar 

  15. Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020;587(7835):567–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Poole K, Herget R, Lapatsina L, Ngo HD, Lewin GR. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat Commun. 2014;5:3520.

    Article  PubMed  CAS  Google Scholar 

  17. Qi Y, Andolfi L, Frattini F, Mayer F, Lazzarino M, Hu J. Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons. Nat Commun. 2015;6:8512.

    Article  CAS  PubMed  Google Scholar 

  18. Friedrich EE, Hong Z, **ong S, et al. Endothelial cell Piezo1 mediates pressure-induced lung vascular hyperpermeability via disruption of adherens junctions. Proc Natl Acad Sci USA. 2019;116(26):12980–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Iring A, ** YJ, Albarran-Juarez J, et al. Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure. J Clin Invest. 2019;129(7):2775–91.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zeng WZ, Marshall KL, Min S, et al. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science. 2018;362(6413):464–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Albarrán-Juárez J, Iring A, Wang S, et al. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation. J Exp Med. 2018;215(10):2655–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Morozumi W, Inagaki S, Iwata Y, Nakamura S, Hara H, Shimazawa M. Piezo channel plays a part in retinal ganglion cell damage. Exp Eye Res. 2020;191: 107900.

    Article  CAS  PubMed  Google Scholar 

  23. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86(2):238–42.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhang Y, Li SZ, Li L, He MG, Thomas R, Wang NL. Quantitative analysis of iris changes following mydriasis in subjects with different mechanisms of angle closure. Invest Ophthalmol Vis Sci. 2015;56(1):563–70.

    Article  PubMed  Google Scholar 

  25. Eriksson A, Svedbergh B. Transcellular aqueous humor outflow: a theoretical and experimental study. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1980;212(3–4):187–97.

    Article  CAS  PubMed  Google Scholar 

  26. Sherwood JM, Stamer WD, Overby DR. A model of the oscillatory mechanical forces in the conventional outflow pathway. J R Soc Interface. 2019;16(150):20180652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li P, Reif R, Zhi Z, et al. Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo nonhuman primate eyes. J Biomed Opt. 2012;17(7): 076026.

    Article  PubMed  Google Scholar 

  28. Johnstone M, Martin E, Jamil A. Pulsatile flow into the aqueous veins: manifestations in normal and glaucomatous eyes. Exp Eye Res. 2011;92(5):318–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McDonnell F, Perkumas KM, Ashpole NE, et al. Shear stress in Schlemm’s canal as a sensor of intraocular pressure. Sci Rep. 2020;10(1):5804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Peier AM, Moqrich A, Hergarden AC, et al. A TRP channel that senses cold stimuli and menthol. Cell. 2002;108(5):705–15.

    Article  CAS  PubMed  Google Scholar 

  31. Dubin AE, Murthy S, Lewis AH, et al. Endogenous Piezo1 can confound mechanically activated channel identification and characterization. Neuron. 2017;94(2):266-270.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ranade SS, Syeda R, Patapoutian A. Mechanically activated ion channels. Neuron. 2015;87(6):1162–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Syeda R, Florendo MN, Cox CD, et al. Piezo1 channels are inherently mechanosensitive. Cell Rep. 2016;17(7):1739–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li J, Hou B, Tumova S, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515(7526):279–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ranade SS, Qiu Z, Woo SH, et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci USA. 2014;111(28):10347–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Retailleau K, Duprat F, Arhatte M, et al. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep. 2015;13(6):1161–71.

    Article  CAS  PubMed  Google Scholar 

  37. Wang S, Iring A, Strilic B, et al. P2Y(2) and Gq/G(1)(1) control blood pressure by mediating endothelial mechanotransduction. J Clin Invest. 2015;125(8):3077–86.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Larsen FL, Katz S, Roufogalis BD, Brooks DE. Physiological shear stresses enhance the Ca2+ permeability of human erythrocytes. Nature. 1981;294(5842):667–8.

    Article  CAS  PubMed  Google Scholar 

  39. Lew VL, Daw N, Perdomo D, Etzion Z, Bookchin RM, Tiffert T. Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells. Blood. 2003;102(12):4206–13.

    Article  CAS  PubMed  Google Scholar 

  40. Zarychanski R, Schulz VP, Houston BL, et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood. 2012;120(9):1908–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Andolfo I, Alper SL, De Franceschi L, et al. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood. 2013;121(19):3925–35.

    Article  CAS  PubMed  Google Scholar 

  42. Bae C, Gnanasambandam R, Nicolai C, Sachs F, Gottlieb PA. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc Natl Acad Sci USA. 2013;110(12):E1162–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Albuisson J, Murthy SE, Bandell M, et al. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat Commun. 2013;4:1884.

    Article  PubMed  CAS  Google Scholar 

  44. Cahalan SM, Lukacs V, Ranade SS, Chien S, Bandell M, Patapoutian A. Piezo1 links mechanical forces to red blood cell volume. Elife. 2015. https://doi.org/10.7554/eLife.07370.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Fotiou E, Martin-Almedina S, Simpson MA, et al. Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat Commun. 2015;6:8085.

    Article  PubMed  Google Scholar 

  46. Lukacs V, Mathur J, Mao R, et al. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nat Commun. 2015;6:8329.

    Article  CAS  PubMed  Google Scholar 

  47. Solis AG, Bielecki P, Steach HR, et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature. 2019;573(7772):69–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shen B, Tasdogan A, Ubellacker JM, et al. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature. 2021;591(7850):438–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sun W, Chi S, Li Y, et al. The mechanosensitive Piezo1 channel is required for bone formation. eLife. 2019;8, e7454.

  50. Li X, Han L, Nookaew I, Mannen E, Silva MJ, Almeida M, **ong J. Stimulation of piezo1 by mechanical signals promotes bone anabolism. Elife. 2019. https://doi.org/10.7554/eLife.49631.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Gudipaty SA, Lindblom J, Loftus PD, et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017;543(7643):118–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Eisenhoffer GT, Loftus PD, Yoshigi M, et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature. 2012;484(7395):546–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Spier I, Kerick M, Drichel D, et al. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis. Fam Cancer. 2016;15(2):281–8.

    Article  CAS  PubMed  Google Scholar 

  54. Chen X, Wanggou S, Bodalia A, et al. A feedforward mechanism mediated by mechanosensitive ion channel PIEZO1 and tissue mechanics promotes glioma aggression. Neuron. 2018;100(4):799–815.

  55. Martins JR, Penton D, Peyronnet R, et al. Piezo1-dependent regulation of urinary osmolarity. Pflugers Arch. 2016;468(7):1197–206.

    Article  CAS  PubMed  Google Scholar 

  56. Buffault J, Labbe A, Hamard P, Brignole-Baudouin F, Baudouin C. The trabecular meshwork: Structure, function and clinical implications. A review of the literature. J Fr Ophtalmol. 2020;43(7):e217–e30.

  57. Stamer WD, Clark AF. The many faces of the trabecular meshwork cell. Exp Eye Res. 2017;158:112–23.

    Article  CAS  PubMed  Google Scholar 

  58. Vranka JA, Kelley MJ, Acott TS, Keller KE. Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma. Exp Eye Res. 2015;133:112–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Weinreb RN, Robinson MR, Dibas M, Stamer WD. Matrix metalloproteinases and glaucoma treatment. J Ocul Pharmacol Ther. 2020;36(4):208–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Keller KE, Aga M, Bradley JM, Kelley MJ, Acott TS. Extracellular matrix turnover and outflow resistance. Exp Eye Res. 2009;88(4):676–82.

    Article  CAS  PubMed  Google Scholar 

  61. Last JA, Pan T, Ding Y, et al. Elastic modulus determination of normal and glaucomatous human trabecular meshwork. Invest Ophthalmol Vis Sci. 2011;52(5):2147–52.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Yemanyi F, Raghunathan V. Lysophosphatidic acid and IL-6 trans-signaling interact via YAP/TAZ and STAT3 signaling pathways in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2020;61(13):29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Li G, Lee C, Read AT, et al. Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis. eLife. 2021;10, e60831.

  64. Liu Z, Li S, Qian X, Li L, Zhang H, Liu Z. RhoA/ROCK-YAP/TAZ axis regulates the fibrotic activity in dexamethasone-treated human trabecular meshwork cells. Front Mol Biosci. 2021;8: 728932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Alvarado J, Murphy C, Juster R. Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology. 1984;91(6):564–79.

    Article  CAS  PubMed  Google Scholar 

  66. Rohen JW, Witmer R. Electrn microscopic studies on the trabecular meshwork in glaucoma simplex. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1972;183(4):251–66.

    Article  CAS  PubMed  Google Scholar 

  67. Tektas OY, Lutjen-Drecoll E. Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp Eye Res. 2009;88(4):769–75.

    Article  CAS  PubMed  Google Scholar 

  68. Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res. 2009;88(4):648–55.

    Article  CAS  PubMed  Google Scholar 

  69. Yarishkin O, Phuong TTT, Bretz CA, Olsen KW, Baumann JM, Lakk M, et al. TREK-1 channels regulate pressure sensitivity and calcium signaling in trabecular meshwork cells. J Gen Physiol. 2018;150(12):1660–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hamanaka T, Kasahara K, Takemura T. Histopathology of the trabecular meshwork and Schlemm’s canal in primary angle-closure glaucoma. Invest Ophthalmol Vis Sci. 2011;52(12):8849–61.

    Article  PubMed  Google Scholar 

  71. Sihota R, Goyal A, Kaur J, Gupta V, Nag TC. Scanning electron microscopy of the trabecular meshwork: understanding the pathogenesis of primary angle closure glaucoma. Indian J Ophthalmol. 2012;60(3):183–8.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Rao PV, Pattabiraman PP, Kopczynski C. Role of the Rho GTPase/Rho kinase signaling pathway in pathogenesis and treatment of glaucoma: Bench to bedside research. Exp Eye Res. 2017;158:23–32.

    Article  CAS  PubMed  Google Scholar 

  73. Kusuhara S, Nakamura M. Ripasudil hydrochloride hydrate in the treatment of glaucoma: safety, efficacy, and patient selection. Clin Ophthalmol. 2020;14:1229–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Coste B, Crest M, Delmas P. Pharmacological dissection and distribution of NaN/Nav1.9, T-type Ca2+ currents, and mechanically activated cation currents in different populations of DRG neurons. J Gen Physiol. 2007;129(1):57–77.

  75. Drew LJ, Wood JN, Cesare P. Distinct mechanosensitive properties of capsaicin-sensitive and -insensitive sensory neurons. J Neurosci. 2002;22(12):RC228.

  76. Hu J, Lewin GR. Mechanosensitive currents in the neurites of cultured mouse sensory neurones. J Physiol. 2006;577(Pt 3):815–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Drew LJ, Rohrer DK, Price MP, et al. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol. 2004;556(Pt 3):691–710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Drew LJ, Rugiero F, Cesare P, et al. High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. PLoS One. 2007;2(6): e515.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Wetzel C, Hu J, Riethmacher D, et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature. 2007;445(7124):206–9.

    Article  CAS  PubMed  Google Scholar 

  80. Ramos RF, Sumida GM, Stamer WD. Cyclic mechanical stress and trabecular meshwork cell contractility. Invest Ophthalmol Vis Sci. 2009;50(8):3826–32.

    Article  PubMed  Google Scholar 

  81. Liton PB, Gonzalez P. Stress response of the trabecular meshwork. J Glaucoma. 2008;17(5):378–85.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Tran VT, Ho PT, Cabrera L, Torres JE, Bhattacharya SK. Mechanotransduction channels of the trabecular meshwork. Curr Eye Res. 2014;39(3):291–303.

    Article  CAS  PubMed  Google Scholar 

  83. Uchida T, Shimizu S, Yamagishi R, et al. Mechanical stretch induces Ca2+ influx and extracellular release of PGE2 through Piezo1 activation in trabecular meshwork cells. Sci Rep. 2021;11(1):4044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhu W, Hou F, Fang J, et al. The role of Piezo1 in conventional aqueous humor outflow dynamics. iScience. 2021;24(2):102042.

  85. Yarishkin O, Phuong TTT, Baumann JM, et al. Piezo1 channels mediate trabecular meshwork mechanotransduction and promote aqueous fluid outflow. J Physiol. 2021;599(2):571–92.

    Article  CAS  PubMed  Google Scholar 

  86. Patel PD, Chen YL, Kasetti RB, et al. Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma. Proc Natl Acad Sci USA. 2021;118(16).

  87. Burkholder TJ. Mechanotransduction in skeletal muscle. Front Biosci. 2007;12:174–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Munaron L. Shuffling the cards in signal transduction: calcium, arachidonic acid and mechanosensitivity. World J Biol Chem. 2011;2(4):59–66.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Saeki T, Ota T, Aihara M, Araie M. Effects of prostanoid EP agonists on mouse intraocular pressure. Invest Ophthalmol Vis Sci. 2009;50(5):2201–8.

    Article  PubMed  Google Scholar 

  90. Kalouche G, Beguier F, Bakria M, et al. Activation of prostaglandin FP and EP2 receptors differently modulates myofibroblast transition in a model of adult primary human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2016;57(4):1816–25.

    Article  CAS  PubMed  Google Scholar 

  91. Kirihara T, Taniguchi T, Yamamura K, et al. Pharmacologic characterization of omidenepag isopropyl, a novel selective EP2 receptor agonist, as an ocular hypotensive agent. Invest Ophthalmol Vis Sci. 2018;59(1):145–53.

    Article  CAS  PubMed  Google Scholar 

  92. Fuwa M, Toris CB, Fan S, et al. Effects of a novel selective EP2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys. J Ocul Pharmacol Ther. 2018;34(7):531–7.

    Article  CAS  PubMed  Google Scholar 

  93. Wang JW, Woodward DF, Stamer WD. Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow. Invest Ophthalmol Vis Sci. 2013;54(7):4782–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Morozumi W, Aoshima K, Inagaki S, et al. Piezo 1 is involved in intraocular pressure regulation. J Pharmacol Sci. 2021;147(2):211–21.

    Article  CAS  PubMed  Google Scholar 

  95. Kang H, Hong Z, Zhong M, et al. Piezo1 mediates angiogenesis through activation of MT1-MMP signaling. Am J Physiol Cell Physiol. 2019;316(1):C92–103.

    Article  CAS  PubMed  Google Scholar 

  96. Bae C, Sachs F, Gottlieb PA. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry. 2011;50(29):6295–300.

    Article  CAS  PubMed  Google Scholar 

  97. Inoue R, Jian Z, Kawarabayashi Y. Mechanosensitive TRP channels in cardiovascular pathophysiology. Pharmacol Ther. 2009;123(3):371–85.

    Article  CAS  PubMed  Google Scholar 

  98. Suchyna TM. Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology. Prog Biophys Mol Biol. 2017;130(Pt B):244–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Friedrich O, Wagner S, Battle AR, Schürmann S, Martinac B. Mechano-regulation of the beating heart at the cellular level--mechanosensitive channels in normal and diseased heart. Progress in biophysics and molecular biology.2012;110(2–3), 226–238.

  100. Gnanasambandam R, Ghatak C, Yasmann A, et al. GsMTx4: mechanism of inhibiting mechanosensitive ion channels. Biophys J. 2017;112(1):31–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Li AF, Tane N, Roy S. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis. 2004;10:750–7.

    CAS  PubMed  Google Scholar 

  102. Faralli JA, Filla MS, Peters DM. Role of fibronectin in primary open angle glaucoma. Cells. 2019. https://doi.org/10.3390/cells8121518.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Morgan MR, Humphries MJ, Bass MD. Synergistic control of cell adhesion by integrins and syndecans. Nat Rev Mol Cell Biol. 2007;8(12):957–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Choi HJ, Sun D, Jakobs TC. Astrocytes in the optic nerve head express putative mechanosensitive channels. Mol Vis. 2015;21:749–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Almasieh M, Wilson AM, Morquette B, Cueva Vargas JL, Di Polo A. The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res. 2012;31(2):152–81.

    Article  CAS  PubMed  Google Scholar 

  106. Ooashi N, Futatsugi A, Yoshihara F, Mikoshiba K, Kamiguchi H. Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3. J Cell Biol. 2005;170(7):1159–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Page M, Pacico N, Ourtioualous S, Deprez T, Koshibu K. Procognitive compounds promote neurite outgrowth. Pharmacology. 2015;96(3–4):131–6.

    Article  CAS  PubMed  Google Scholar 

  108. Jacques-Fricke BT, Seow Y, Gottlieb PA, Sachs F, Gomez TM. Ca2+ influx through mechanosensitive channels inhibits neurite outgrowth in opposition to other influx pathways and release from intracellular stores. J Neurosci Off J Soc Neurosci. 2006;26(21):5656–64.

    Article  CAS  Google Scholar 

  109. Enes J, Langwieser N, Ruschel J, et al. Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons. Curr Biol. 2010;20(13):1154–64.

  110. Tedeschi A, Dupraz S, Laskowski CJ, et al. The calcium channel subunit alpha2delta2 suppresses axon regeneration in the adult CNS. Neuron. 2016;92(2):419–34.

    Article  CAS  PubMed  Google Scholar 

  111. Quigley HA, Addicks EM. Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport. Invest Ophthalmol Vis Sci. 1980;19(2):137–52.

  112. Balaratnasingam C, Morgan WH, Bass L, Matich G, Cringle SJ, Yu DY. Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure. Invest Ophthalmol Vis Sci. 2007;48(8):3632–44.

    Article  PubMed  Google Scholar 

  113. Johansson JO. Inhibition of retrograde axoplasmic transport in rat optic nerve by increased IOP in vitro. Invest Ophthalmol Vis Sci. 1983;24(12):1552–8.

    CAS  PubMed  Google Scholar 

  114. Johansson JO. Inhibition and recovery of retrograde axoplasmic transport in rat optic nerve during and after elevated IOP in vivo. Exp Eye Res. 1988;46(2):223–7.

    Article  CAS  PubMed  Google Scholar 

  115. McHugh BJ, Buttery R, Lad Y, Banks S, Haslett C, Sethi T. Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum. J Cell Sci. 2010;123(Pt 1):51–61.

    Article  PubMed  Google Scholar 

  116. McHugh BJ, Murdoch A, Haslett C, Sethi T. Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration. PLoS One. 2012;7(7): e40346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yang XN, Lu YP, Liu JJ, et al. Piezo1 is as a novel trefoil factor family 1 binding protein that promotes gastric cancer cell mobility in vitro. Dig Dis Sci. 2014;59(7):1428–35.

    Article  CAS  PubMed  Google Scholar 

  118. Hernandez MR. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 2000;19(3):297–321.

    Article  CAS  PubMed  Google Scholar 

  119. Lye-Barthel M, Sun D, Jakobs TC. Morphology of astrocytes in a glaucomatous optic nerve. Invest Ophthalmol Vis Sci. 2013;54(2):909–17.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Liu J, Yang Y, Liu Y. Piezo1 plays a role in optic nerve head astrocyte reactivity. Exp Eye Res. 2021;204: 108445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Tehrani S, Johnson EC, Cepurna WO, Morrison JC. Astrocyte processes label for filamentous actin and reorient early within the optic nerve head in a rat glaucoma model. Invest Ophthalmol Vis Sci. 2014;55(10):6945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tehrani S, Davis L, Cepurna WO, et al. Optic nerve head astrocytes display axon-dependent and -independent reactivity in response to acutely elevated intraocular pressure. Invest Ophthalmol Vis Sci. 2019;60(1):312–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Niggel J, Sigurdson W, Sachs F. Mechanically induced calcium movements in astrocytes, bovine aortic endothelial cells and C6 glioma cells. J Membr Biol. 2000;174(2):121–34.

    Article  CAS  PubMed  Google Scholar 

  124. Ostrow LW, Suchyna TM, Sachs F. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs). Biochem Biophys Res Commun. 2011;410(1):81–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Resta V, Novelli E, Vozzi G, et al. Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP. Eur J Neurosci. 2007;25(9):2741–54.

    Article  PubMed  Google Scholar 

  126. Reigada D, Lu W, Zhang M, Mitchell CH. Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels. Neuroscience. 2008;157(2):396–404.

    Article  CAS  PubMed  Google Scholar 

  127. Chauhan BC. Endothelin and its potential role in glaucoma. Can J Ophthalmol. 2008;43(3):356–60.

    Article  PubMed  Google Scholar 

  128. Lazzara F, Amato R, Platania CBM, et al. 1alpha,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice. J Neuroinflammation. 2021;18(1):206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Olabiyi AA, Passos DF, da Silva JLG, Schetinger MRC, Rosa Leal DB. Role of purinergic system and vitamin D in the anti-cancer immune response. Life Sci. 2021;287: 120110.

    Article  CAS  PubMed  Google Scholar 

  130. Song Y, Li D, Farrelly O, et al. The Mechanosensitive ion channel Piezo inhibits axon regeneration. Neuron. 2019;102(2):373–89.

  131. Pfister BJ, Iwata A, Meaney DF, Smith DH. Extreme stretch growth of integrated axons. J Neurosci. 2004;24(36):7978–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Smith DH. Stretch growth of integrated axon tracts: extremes and exploitations. Prog Neurobiol. 2009;89(3):231–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Suter DM, Miller KE. The emerging role of forces in axonal elongation. Prog Neurobiol. 2011;94(2):91–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Koser DE, Thompson AJ, Foster SK, et al. Mechanosensing is critical for axon growth in the develo** brain. Nat Neurosci. 2016;19(12):1592–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Coste B, Murthy SE, Mathur J, et al. Piezo1 ion channel pore properties are dictated by C-terminal region. Nat Commun. 2015;6:7223.

    Article  PubMed  Google Scholar 

  136. Li F, Lo TY, Miles L, et al. The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation. Nat Commun. 2021;12(1):3845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Li H. TRP channel classification. Adv Exp Med Biol. 2017;976:1–8.

    Article  CAS  PubMed  Google Scholar 

  138. Miyamoto T, Mochizuki T, Nakagomi H, et al. Functional role for Piezo1 in stretch-evoked Ca(2)(+) influx and ATP release in urothelial cell cultures. J Biol Chem. 2014;289(23):16565–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Adapala RK, Thoppil RJ, Luther DJ, et al. TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals. J Mol Cell Cardiol. 2013;54:45–52.

    Article  CAS  PubMed  Google Scholar 

  140. Ryskamp DA, Frye AM, Phuong TT, et al. TRPV4 regulates calcium homeostasis, cytoskeletal remodeling, conventional outflow and intraocular pressure in the mammalian eye. Sci Rep. 2016;6:30583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Sharma S, Goswami R, Zhang DX, Rahaman SO. TRPV4 regulates matrix stiffness and TGFβ1-induced epithelial-mesenchymal transition. J Cell Mol Med. 2019;23(2):761–74.

    Article  CAS  PubMed  Google Scholar 

  142. Luo N, Conwell MD, Chen X, et al. Primary cilia signaling mediates intraocular pressure sensation. Proc Natl Acad Sci USA. 2014;111(35):12871–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Prosseda PP, Alvarado JA, Wang B, et al. Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation. Sci Adv. 2020;6(18):eaay8699.

  144. Lakk M, Krizaj D. TRPV4-Rho signaling drives cytoskeletal and focal adhesion remodeling in trabecular meshwork cells. Am J Physiol Cell Physiol. 2021;320(6):C1013–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Turner DC, Edmiston AM, Zohner YE, et al. Transient intraocular pressure fluctuations: source, magnitude, frequency, and associated mechanical energy. Invest Ophthalmol Vis Sci. 2019;60(7):2572–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Swain SM, Romac JM, Shahid RA, et al. TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation. J Clin Invest. 2020;130(5):2527–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Peyronnet R, Martins JR, Duprat F, et al. Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep. 2013;14(12):1143–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Gilliam JC, Wensel TG. TRP channel gene expression in the mouse retina. Vision Res. 2011;51(23–24):2440–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Leonelli M, Martins DO, Kihara AH, Britto LR. Ontogenetic expression of the vanilloid receptors TRPV1 and TRPV2 in the rat retina. Int J Dev Neurosci. 2009;27(7):709–18.

    Article  CAS  PubMed  Google Scholar 

  150. Ryskamp DA, Witkovsky P, Barabas P, et al. The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells. J Neurosci. 2011;31(19):7089–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Sap**ton RM, Sidorova T, Long DJ, Calkins DJ. TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure. Invest Ophthalmol Vis Sci. 2009;50(2):717–28.

    Article  PubMed  Google Scholar 

  152. Ward NJ, Ho KW, Lambert WS, Weitlauf C, Calkins DJ. Absence of transient receptor potential vanilloid-1 accelerates stress-induced axonopathy in the optic projection. J Neurosci. 2014;34(9):3161–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Weitlauf C, Ward NJ, Lambert WS, et al. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation. J Neurosci. 2014;34(46):15369–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Ryskamp DA, Jo AO, Frye AM, et al. Swelling and eicosanoid metabolites differentially gate TRPV4 channels in retinal neurons and glia. J Neurosci. 2014;34(47):15689–700.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Meadows HJ, Benham CD, Cairns W, et al. Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. Pflugers Arch. 2000;439(6):714–22.

    Article  CAS  PubMed  Google Scholar 

  156. Carreon T, van der Merwe E, Fellman RL, Johnstone M, Bhattacharya SK. Aqueous outflow—a continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res. 2017;57:108–33.

    Article  PubMed  Google Scholar 

  157. Yarishkin O, Phuong TTT, Krizaj D. Trabecular meshwork TREK-1 channels function as polymodal integrators of pressure and pH. Invest Ophthalmol Vis Sci. 2019;60(6):2294–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Abad E, Lorente G, Gavara N, Morales M, Gual A, Gasull X. Activation of store-operated Ca(2+) channels in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2008;49(2):677–86.

    Article  PubMed  Google Scholar 

  159. Lepple-Wienhues A, Stahl F, Willner U, Schafer R, Wiederholt M. Endothelin-evoked contractions in bovine ciliary muscle and trabecular meshwork: interaction with calcium, nifedipine and nickel. Curr Eye Res. 1991;10(10):983–9.

    Article  CAS  PubMed  Google Scholar 

  160. Yarishkin O, Baumann JM, Krizaj D. Mechano-electrical transduction in trabecular meshwork involves parallel activation of TRPV4 and TREK-1 channels. Channels (Austin). 2019;13(1):168–71.

    Article  Google Scholar 

  161. Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, et al. Chemical activation of the mechanotransduction channel piezo1. Elife. 2015. https://doi.org/10.7554/eLife.07369.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Botello-Smith WM, Jiang W, Zhang H, et al. A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1. Nat Commun. 2019;10(1):4503.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Wang Y, Chi S, Guo H, et al. A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun. 2018;9(1):1300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. **ao B. Levering mechanically activated piezo channels for potential pharmacological intervention. Annu Rev Pharmacol Toxicol. 2020;60:195–218.

    Article  CAS  PubMed  Google Scholar 

  165. Shi J, Hyman AJ, De Vecchis D, et al. Sphingomyelinase disables inactivation in endogenous PIEZO1 channels. Cell Rep. 2020;33(1): 108225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Cox CD, Bae C, Ziegler L, et al. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat Commun. 2016;7:10366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Pathak MM, Nourse JL, Tran T, et al. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc Natl Acad Sci USA. 2014;111(45):16148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Matsuo T, Matsuo N. Intracellular calcium response to hydraulic pressure in human trabecular cells. Br J Ophthalmol. 1996;80(6):561–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Tumminia SJ, Mitton KP, Arora J, Zelenka P, Epstein DL, Russell P. Mechanical stretch alters the actin cytoskeletal network and signal transduction in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1998;39(8):1361–71.

    CAS  PubMed  Google Scholar 

  170. He Y, Ge J, Tombran-Tink J. Mitochondrial defects and dysfunction in calcium regulation in glaucomatous trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2008;49(11):4912–22.

    Article  PubMed  Google Scholar 

  171. Wiederholt M, Thieme H, Stumpff F. The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res. 2000;19(3):271–95.

    Article  CAS  PubMed  Google Scholar 

  172. Fernandez-Durango R, Fernandez-Martinez A, Garcia-Feijoo J, et al. Expression of nitrotyrosine and oxidative consequences in the trabecular meshwork of patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2008;49(6):2506–11.

    Article  PubMed  Google Scholar 

  173. Stamer WD, Lei Y, Boussommier-Calleja A, Overby DR, Ethier CR. eNOS, a pressure-dependent regulator of intraocular pressure. Invest Ophthalmol Vis Sci. 2011;52(13):9438–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Chang JY, Stamer WD, Bertrand J, et al. Role of nitric oxide in murine conventional outflow physiology. Am J Physiol Cell Physiol. 2015;309(4):C205–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Dismuke WM, Mbadugha CC, Ellis DZ. NO-induced regulation of human trabecular meshwork cell volume and aqueous humor outflow facility involve the BKCa ion channel. Am J Physiol Cell Physiol. 2008;294(6):C1378–86.

    Article  CAS  PubMed  Google Scholar 

  176. Kotikoski H, Alajuuma P, Moilanen E, et al. Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: role of cyclic GMP. J Ocul Pharmacol Ther. 2002;18(1):11–23.

    Article  CAS  PubMed  Google Scholar 

  177. Heyne GW, Kiland JA, Kaufman PL, Gabelt BT. Effect of nitric oxide on anterior segment physiology in monkeys. Invest Ophthalmol Vis Sci. 2013;54(7):5103–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  178. Marziano C, EL HongK Cope, Kotlikoff MI, Isakson BE, Sonkusare SK. Nitric oxide-dependent feedback loop regulates transient receptor potential vanilloid 4 (TRPV4) channel cooperativity and endothelial function in small pulmonary arteries. J Am Heart Assoc. 2017;6(12):e007157. https://doi.org/10.1161/JAHA.117.007157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Hill-Eubanks DC, Gonzales AL, Sonkusare SK, Nelson MT. Vascular TRP channels: performing under pressure and going with the flow. Physiology (Bethesda). 2014;29(5):343–60.

    CAS  Google Scholar 

  180. Cabral PD, Garvin JL. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb. Am J Physiol Renal Physiol. 2014;307(6):F666–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Sukumaran SV, Singh TU, Parida S, et al. TRPV4 channel activation leads to endothelium-dependent relaxation mediated by nitric oxide and endothelium-derived hyperpolarizing factor in rat pulmonary artery. Pharmacol Res. 2013;78:18–27.

    Article  CAS  PubMed  Google Scholar 

  182. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37, 37a–37d.

  183. Wu RY, Ma N. Expression of nitric oxide synthase and guanylate cyclase in the human ciliary body and trabecular meshwork. Chin Med J (Engl). 2012;125(1):129–33.

    CAS  Google Scholar 

  184. Dismuke WM, Liang J, Overby DR, Stamer WD. Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility. Exp Eye Res. 2014;120:28–35.

    Article  CAS  PubMed  Google Scholar 

  185. Schmetterer L, Polak K. Role of nitric oxide in the control of ocular blood flow. Prog Retin Eye Res. 2001;20(6):823–47.

    Article  CAS  PubMed  Google Scholar 

  186. Kim JW. Comparative study of the effects of trabecular meshwork outflow drugs on the permeability and nitric oxide production in trabecular meshwork cells. Korean J Ophthalmol. 2017;31(5):452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Moreno-Lopez B. Local isoform-specific NOS inhibition: a promising approach to promote motor function recovery after nerve injury. J Neurosci Res. 2010;88(9):1846–57.

    CAS  PubMed  Google Scholar 

  188. Rabinovich D, Yaniv SP, Alyagor I, Schuldiner O. Nitric oxide as a switching mechanism between axon degeneration and regrowth during developmental remodeling. Cell. 2016;164(1–2):170–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Risinger M, Kalfa TA. Red cell membrane disorders: structure meets function. Blood. 2020;136(11):1250–61.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Baxter SL, Keenan WT, Athanas AJ, et al. Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice. Sci Rep. 2020;10(1):19013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Duchemin AL, Vignes H, Vermot J. Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis. eLife. 2019;8, e44706.

  192. Borbiro I, Rohacs T. Regulation of Piezo channels by cellular signaling pathways. Curr Top Membr. 2017;79:245–61.

    Article  CAS  PubMed  Google Scholar 

  193. Zhang Y, Li SZ, Li L, He MG, Thomas R, Wang NL. Dynamic iris changes as a risk factor in primary angle closure disease. Invest Ophthalmol Vis Sci. 2016;57(1):218–26.

    Article  CAS  PubMed  Google Scholar 

  194. Xu G, Chen Z. Corneal hysteresis as a risk factor for optic nerve head surface depression and retinal nerve fiber layer thinning in glaucoma patients. Sci Rep. 2021;11(1):11677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Safa BN, Wong CA, Ha J, Ethier CR. Glaucoma and biomechanics. Curr Opin Ophthalmol. 2022;33(2):80–90.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank members of the Department of Ophthalmology of the Fourth Affiliated Hospital of Harbin Medical University who contributed to and supported this study. This work was supported by the Natural Science Grant of Heilongjiang Province of China (H2018035, LH2020H040), the innovation and development foundation of the First Affiliated Hospital of Harbin Medical University (2018L002) and the special grant of the Fourth Affiliated Hospital of Harbin Medical University (HYDSYTB202209).

Funding

This work was supported by the Natural Science Grant of Heilongjiang Province of China (H2018035, LH2020H040) and the Innovation and Development Foundation of the First Affiliated Hospital of Harbin Medical University (2018L002).

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  1. Ying Su and Feng Wang contributed equally to this work and worked as co-corresponding authors.

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  1. Department of Ophthalmology, Fourth Affiliated Hospital, Harbin Medical University, Yiyuan Road, Harbin, 150001, China

    Yidan Chen & Feng Wang

  2. Eye Hospital, First Affiliated Hospital, Harbin Medical University, Yiman Road, Harbin, 150007, China

    Ying Su

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Chen, Y., Su, Y. & Wang, F. The Piezo1 ion channel in glaucoma: a new perspective on mechanical stress. Human Cell 35, 1307–1322 (2022). https://doi.org/10.1007/s13577-022-00738-w

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