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Glaucoma

Simvastatin Attenuates Glucocorticoid-Induced Human Trabecular Meshwork Cell Dysfunction via YAP/TAZ Inactivation

, , , , , & ORCID Icon show all
Pages 736-749 | Received 07 Nov 2022, Accepted 18 Apr 2023, Published online: 07 May 2023

References

  • Brubaker RF. Flow of aqueous humor in humans [The Friedenwald Lecture]. Invest Ophthalmol Vis Sci. 1991;32(13):3145–3166.
  • Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res. 2009;88(4):648–655. doi:10.1016/j.exer.2009.02.007.
  • Tamm ER, Braunger BM, Fuchshofer R. Intraocular pressure and the mechanisms involved in resistance of the aqueous humor flow in the trabecular meshwork outflow pathways. Prog Mol Biol Transl Sci. 2015;134:301–314. doi:10.1016/bs.pmbts.2015.06.007.
  • Stamer WD, Clark AF. The many faces of the trabecular meshwork cell. Exp Eye Res. 2017;158:112–123. doi:10.1016/j.exer.2016.07.009.
  • Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res. 2008;86(4):543–561. doi:10.1016/j.exer.2008.01.013.
  • Kelley MJ, Rose AY, Keller KE, Hessle H, Samples JR, Acott TS. Stem cells in the trabecular meshwork: present and future promises. Exp Eye Res. 2009;88(4):747–751. doi:10.1016/j.exer.2008.10.024.
  • Kwon YH, Fingert JH, Kuehn MH, Alward WL. Primary open-angle glaucoma. N Engl J Med. 2009;360(11):1113–1124. doi:10.1056/NEJMra0804630.
  • Wang K, Read AT, Sulchek T, Ethier CR. Trabecular meshwork stiffness in glaucoma. Exp Eye Res. 2017;158:3–12. doi:10.1016/j.exer.2016.07.011.
  • Stamer WD, Acott TS. Current understanding of conventional outflow dysfunction in glaucoma. Curr Opin Ophthalmol. 2012;23(2):135–143. doi:10.1097/ICU.0b013e32834ff23e.
  • Acott TS, Vranka JA, Keller KE, Raghunathan V, Kelley MJ. Normal and glaucomatous outflow regulation. Prog Retin Eye Res. 2021;82:100897. doi:10.1016/j.preteyeres.2020.100897.
  • Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, others, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474(7350):179–183. and doi:10.1038/nature10137.
  • Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev. 2014;94(4):1287–1312. doi:10.1152/physrev.00005.2014.
  • Varelas X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development. 2014;141(8):1614–1626. doi:10.1242/dev.102376.
  • Panciera T, Azzolin L, Cordenonsi M, Piccolo S. Mechanobiology of YAP and TAZ in physiology and disease. Nat Rev Mol Cell Biol. 2017;18(12):758–770. doi:10.1038/nrm.2017.87.
  • Li H, Raghunathan V, Stamer WD, Ganapathy PS, Herberg S. Extracellular matrix stiffness and TGFbeta2 regulate YAP/TAZ activity in human trabecular meshwork cells. Front Cell Dev Biol. 2022;10:844342. doi:10.3389/fcell.2022.844342.
  • Yemanyi F, Vranka J, Raghunathan VK. Crosslinked extracellular matrix stiffens human trabecular meshwork cells Via dysregulating beta-catenin and YAP/TAZ signaling pathways. Invest Ophthalmol Vis Sci. 2020;61(10):41. doi:10.1167/iovs.61.10.41.
  • Peng J, Wang H, Wang X, Sun M, Deng S, Wang Y. YAP and TAZ mediate steroid-induced alterations in the trabecular meshwork cytoskeleton in human trabecular meshwork cells. Int J Mol Med. 2018;41(1):164–172. doi:10.3892/ijmm.2017.3207.
  • Chen WS, Cao Z, Krishnan C, Panjwani N. Verteporfin without light stimulation inhibits YAP activation in trabecular meshwork cells: implications for glaucoma treatment. Biochem Biophys Res Commun. 2015;466(2):221–225. doi:10.1016/j.bbrc.2015.09.012.
  • Ho LTY, Skiba N, Ullmer C, Rao PV. Lysophosphatidic acid induces ECM production via activation of the mechanosensitive YAP/TAZ transcriptional pathway in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2018;59(5):1969–1984. doi:10.1167/iovs.17-23702.
  • Dhamodaran K, Baidouri H, Sandoval L, Raghunathan V. Wnt activation after inhibition restores trabecular meshwork cells toward a normal phenotype. Invest Ophthalmol Vis Sci. 2020;61(6):30. doi:10.1167/iovs.61.6.30.
  • 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. doi:10.1167/iovs.61.13.29.
  • Thomasy SM, Morgan JT, Wood JA, Murphy CJ, Russell P. Substratum stiffness and latrunculin B modulate the gene expression of the mechanotransducers YAP and TAZ in human trabecular meshwork cells. Exp Eye Res. 2013;113:66–73. doi:10.1016/j.exer.2013.05.014.
  • Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, Ong JS, Hewitt AW, Segrè AV, Rouhana JM, others, et al. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat Commun. 2021;12(1):1258. and doi:10.1038/s41467-020-20851-4.
  • Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3–11. doi:10.1016/j.phrs.2014.03.002.
  • DeBose-Boyd RA. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 2008;18(6):609–621. doi:10.1038/cr.2008.61.
  • Posch-Pertl L, Michelitsch M, Wagner G, Wildner B, Silbernagel G, Pregartner G, Wedrich A. Cholesterol and glaucoma: a systematic review and meta-analysis. Acta Ophthalmol. 2022;100(2):148–158. doi:10.1111/aos.14769.
  • Wang S, Bao X. Hyperlipidemia, blood lipid level, and the risk of glaucoma: a meta-analysis. Invest Ophthalmol Vis Sci. 2019;60(4):1028–1043. doi:10.1167/iovs.18-25845.
  • McGwin G, Jr., McNeal S, Owsley C, Girkin C, Epstein D, Lee PP. Statins and other cholesterol-lowering medications and the presence of glaucoma. Arch Ophthalmol. 2004;122(6):822–826. doi:10.1001/archopht.122.6.822.
  • Talwar N, Musch DC, Stein JD. Association of daily dosage and type of statin agent with risk of open-angle glaucoma. JAMA Ophthalmol. 2017;135(3):263–267. doi:10.1001/jamaophthalmol.2016.5406.
  • De Castro DK, Punjabi OS, Bostrom AG, Stamper RL, Lietman TM, Ray K, Lin SC. Effect of statin drugs and aspirin on progression in open-angle glaucoma suspects using confocal scanning laser ophthalmoscopy. Clin Exp Ophthalmol. 2007;35(6):506–513. doi:10.1111/j.1442-9071.2007.01529.x.
  • McCann P, Hogg RE, Fallis R, Azuara-Blanco A. The effect of statins on intraocular pressure and on the incidence and progression of glaucoma: A systematic review and meta-analysis. Invest Ophthalmol Vis Sci. 2016;57(6):2729–2748. doi:10.1167/iovs.15-18595.
  • Stein JD, Newman-Casey PA, Talwar N, Nan B, Richards JE, Musch DC. The relationship between statin use and open-angle glaucoma. Ophthalmology. 2012;119(10):2074–2081. doi:10.1016/j.ophtha.2012.04.029.
  • Thiermeier N, Lammer R, Mardin C, Hohberger B. Erlanger glaucoma registry: effect of a long-term therapy with statins and acetyl salicylic acid on glaucoma conversion and progression. Biology. 2021;10(6):538. doi:10.3390/biology10060538.
  • Song J, Deng PF, Stinnett SS, Epstein DL, Rao PV. Effects of cholesterol-lowering statins on the aqueous humor outflow pathway. Invest Ophthalmol Vis Sci. 2005;46(7):2424–2432. doi:10.1167/iovs.04-0776.
  • Von Zee CL, Richards MP, Bu P, Perlman JI, Stubbs EB. Jr. increased RhoA and RhoB protein accumulation in cultured human trabecular meshwork cells by lovastatin. Invest Ophthalmol Vis Sci. 2009;50(6):2816–2823. doi:10.1167/iovs.08-2466.
  • Von Zee CL, Stubbs EB. Jr. Geranylgeranylation facilitates proteasomal degradation of rho G-proteins in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011;52(3):1676–1683. doi:10.1167/iovs.10-6171.
  • Rodriguez F, Maron DJ, Knowles JW, Virani SS, Lin S, Heidenreich PA. Association between intensity of statin therapy and mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2017;2(1):47–54. doi:10.1001/jamacardio.2016.4052.
  • Song XY, Chen YY, Liu WT, Cong L, Zhang JL, Zhang Y, Zhang YY. Atorvastatin reduces IOP in ocular hypertension in vivo and suppresses ECM in trabecular meshwork perhaps via FGD4. Int J Mol Med. 2022;49(6):76. doi:10.3892/ijmm.2022.5132.
  • Cong L, Fu S, Zhang J, Zhao J, Zhang Y. Effects of atorvastatin on porcine aqueous humour outflow and trabecular meshwork cells. Exp Ther Med. 2018;15(1):210–216. doi:10.3892/etm.2017.5353.
  • Sorrentino G, Ruggeri N, Specchia V, Cordenonsi M, Mano M, Dupont S, Manfrin A, Ingallina E, Sommaggio R, Piazza S, et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol. 2014;16(4):357–366. and doi:10.1038/ncb2936.
  • Oku Y, Nishiya N, Shito T, Yamamoto R, Yamamoto Y, Oyama C, Uehara Y. Small molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers. FEBS Open Bio. 2015;5:542–549. doi:10.1016/j.fob.2015.06.007.
  • Wang K, Li G, Read AT, Navarro I, Mitra AK, Stamer WD, Sulchek T, Ethier CR. The relationship between outflow resistance and trabecular meshwork stiffness in mice. Sci Rep. 2018;8(1):5848. doi:10.1038/s41598-018-24165-w.
  • Jones R, 3rd, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17(2):163–167. doi:10.1097/01.icu.0000193079.55240.18.
  • Raghunathan VK, Morgan JT, Park SA, Weber D, Phinney BS, Murphy CJ, Russell P. Dexamethasone stiffens trabecular meshwork, trabecular meshwork cells, and matrix. Invest Ophthalmol Vis Sci. 2015;56(8):4447–4459. doi:10.1167/iovs.15-16739.
  • Clark AF, Wilson K, McCartney MD, Miggans ST, Kunkle M, Howe W. Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1994;35(1):281–294.
  • Li H, Bagué T, Kirschner A, Strat AN, Roberts H, Weisenthal RW, Patteson AE, Annabi N, Stamer WD, Ganapathy PS, others, et al. A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling. Exp Eye Res. 2021;205:108472. and doi:10.1016/j.exer.2021.108472.
  • Li H, Henty-Ridilla JL, Bernstein AM, Ganapathy PS, Herberg S. TGFbeta2 regulates human trabecular meshwork cell contractility via ERK and ROCK pathways with distinct signaling crosstalk dependent on the culture substrate. Curr Eye Res. 2022;47(8):1165–1178. doi:10.1080/02713683.2022.2071943.
  • Bagué T, Singh A, Ghosh R, Yoo H, Kelly C, deLong MA, Kopczynski CC, Herberg S. Effects of netarsudil-family rho kinase inhibitors on human trabecular meshwork cell contractility and actin remodeling using a bioengineered ECM Hydrogel. Front Ophthalmol. 2022;2:948397. doi:10.3389/fopht.2022.948397.
  • Stamer WD, Seftor RE, Williams SK, Samaha HA, Snyder RW. Isolation and culture of human trabecular meshwork cells by extracellular matrix digestion. Curr Eye Res. 1995;14(7):611–617. doi:10.3109/02713689508998409.
  • Keller KE, Bhattacharya SK, Borrás T, Brunner TM, Chansangpetch S, Clark AF, Dismuke WM, Du Y, Elliott MH, Ethier CR, et al. Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Exp Eye Res. 2018;171:164–173. doi:10.1016/j.exer.2018.03.001.
  • Zhang YN, Avery RK, Vallmajo-Martin Q, Assmann A, Vegh A, Memic A, Olsen BD, Annabi N, Khademhosseini A. A highly elastic and rapidly crosslinkable elastin-like polypeptide-based hydrogel for biomedical applications. Adv Funct Mater. 2015;25(30):4814–4826. doi:10.1002/adfm.201501489.
  • Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, others, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–682. doi:10.1038/nmeth.2019.
  • Timothy P, Lodge PCH. Polymer Chemistry. Boca Raton, FL: CRC Press, 2020. doi:10.1201/9780429190810.
  • Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–1108. doi:10.1038/nprot.2008.73.
  • Kwon H, Kim J, Jho EH. Role of the Hippo pathway and mechanisms for controlling cellular localization of YAP/TAZ. Febs J. 2021;89(19):5798–5818. doi:10.1111/febs.16091.
  • Li H, Singh A, Perkumas KM, Stamer WD, Ganapathy PS, Herberg S. YAP/TAZ mediate TGFβ2-induced Schlemm’s canal cell dysfunction. Invest Ophthalmol Vis Sci. 2022;63(12):15. doi:10.1167/iovs.63.12.15.
  • Tovar-Vidales T, Roque R, Clark AF, Wordinger RJ. Tissue transglutaminase expression and activity in normal and glaucomatous human trabecular meshwork cells and tissues. Invest Ophthalmol Vis Sci. 2008;49(2):622–628. doi:10.1167/iovs.07-0835.
  • Raghunathan VK, Morgan JT, Dreier B, Reilly CM, Thomasy SM, Wood JA, Ly I, Tuyen BC, Hughbanks M, Murphy CJ, et al. Role of substratum stiffness in modulating genes associated with extracellular matrix and mechanotransducers YAP and TAZ. Invest Ophthalmol Vis Sci. 2013;54(1):378–386. and doi:10.1167/iovs.12-11007.
  • Svitkina T. The actin cytoskeleton and actin-based motility. Cold Spring Harb Perspect Biol. 2018;10(1):a018267. doi:10.1101/cshperspect.a018267.
  • Dasgupta I, McCollum D. Control of cellular responses to mechanical cues through YAP/TAZ regulation. J Biol Chem. 2019;294(46):17693–17706. doi:10.1074/jbc.REV119.007963.
  • Wada K, Itoga K, Okano T, Yonemura S, Sasaki H. Hippo pathway regulation by cell morphology and stress fibers. Development. 2011;138(18):3907–3914. doi:10.1242/dev.070987.
  • Mo JS, Yu FX, Gong R, Brown JH, Guan KL. Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev. 2012;26(19):2138–2143. doi:10.1101/gad.197582.112.
  • Wang Z, Wu Y, Wang H, Zhang Y, Mei L, Fang X, Zhang X, Zhang F, Chen H, Liu Y. Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. Proc Natl Acad Sci U S A. 2014;111(1):E89–98. doi:10.1073/pnas.1319190110.
  • Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. MBoC. 2001;12(9):2730–2741. doi:10.1091/mbc.12.9.2730.
  • Tamm ER, Siegner A, Baur A, Lutjen-Drecoll E. Transforming growth factor-beta 1 induces alpha-smooth muscle-actin expression in cultured human and monkey trabecular meshwork. Exp Eye Res. 1996;62(4):389–397. doi:10.1006/exer.1996.0044.
  • Li G, Lee C, Read AT, Wang K, Ha J, Kuhn M, Navarro I, Cui J, Young K, Gorijavolu R. and others. Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis. Elife. 2021;10:e60831. doi:10.7554/eLife.60831.
  • Honjo M, Igarashi N, Nishida J, Kurano M, Yatomi Y, Igarashi K, Kano K, Aoki J, Aihara M. Role of the autotaxin-LPA pathway in dexamethasone-induced fibrotic responses and extracellular matrix production in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2018;59(1):21–30. doi:10.1167/iovs.17-22807.
  • Pattabiraman PP, Rao PV. Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol. 2010;298(3):C749–63. doi:10.1152/ajpcell.00317.2009.
  • Amano M, Nakayama M, Kaibuchi K. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton. 2010;67(9):545–554. doi:10.1002/cm.20472.
  • Wang J, Liu X, Zhong Y. Rho/Rho-associated kinase pathway in glaucoma (review). Int J Oncol. 2013;43(5):1357–1367. doi:10.3892/ijo.2013.2100.
  • Lampi MC, Reinhart-King CA. Targeting extracellular matrix stiffness to attenuate disease: from molecular mechanisms to clinical trials. Sci Transl Med. 2018;10(422):eaao0475. doi:10.1126/scitranslmed.aao0475.
  • Rao PV, Deng P, Sasaki Y, Epstein DL. Regulation of myosin light chain phosphorylation in the trabecular meshwork: role in aqueous humour outflow facility. Exp Eye Res. 2005;80(2):197–206. doi:10.1016/j.exer.2004.08.029.
  • Faralli JA, Schwinn MK, Gonzalez JM, Jr., Filla MS, Peters DM. Functional properties of fibronectin in the trabecular meshwork. Exp Eye Res. 2009;88(4):689–693. doi:10.1016/j.exer.2008.08.019.
  • Faralli JA, Filla MS, Peters DM. Role of Fibronectin in Primary Open Angle Glaucoma. Cells. 2019;8(12):1518. doi:10.3390/cells8121518.
  • Zhou L, Li Y, Yue BY. Glucocorticoid effects on extracellular matrix proteins and integrins in bovine trabecular meshwork cells in relation to glaucoma. Int J Mol Med. 1998;1(2):339–346.
  • Medina-Ortiz WE, Belmares R, Neubauer S, Wordinger RJ, Clark AF. Cellular fibronectin expression in human trabecular meshwork and induction by transforming growth factor-beta2. Invest Ophthalmol Vis Sci. 2013;54(10):6779–6788. doi:10.1167/iovs.13-12298.
  • Tanna AP, Johnson M. Rho/ kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. Ophthalmology. 2018;125(11):1741–1756. doi:10.1016/j.ophtha.2018.04.040.
  • 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. doi:10.1016/j.exer.2016.08.023.
  • Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425–430. doi:10.1038/343425a0.
  • Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem. 1996;271(10):5289–5292. doi:10.1074/jbc.271.10.5289.
  • Tanaka K, Osada H, Murakami-Tonami Y, Horio Y, Hida T, Sekido Y. Statin suppresses Hippo pathway-inactivated malignant mesothelioma cells and blocks the YAP/CD44 growth stimulatory axis. Cancer Lett. 2017;385:215–224. doi:10.1016/j.canlet.2016.10.020.
  • Santos DM, Pantano L, Pronzati G, Grasberger P, Probst CK, Black KE, Spinney JJ, Hariri LP, Nichols R, Lin Y, et al. Screening for YAP inhibitors identifies statins as modulators of fibrosis. Am J Respir Cell Mol Biol. 2020;62(4):479–492. and doi:10.1165/rcmb.2019-0296OC.
  • Totaro A, Panciera T, Piccolo S. YAP/TAZ upstream signals and downstream responses. Nat Cell Biol. 2018;20(8):888–899. doi:10.1038/s41556-018-0142-z.
  • Valon L, Marin-Llaurado A, Wyatt T, Charras G, Trepat X. Optogenetic control of cellular forces and mechanotransduction. Nat Commun. 2017;8(1):14396. doi:10.1038/ncomms14396.
  • Das A, Fischer RS, Pan D, Waterman CM. YAP nuclear localization in the absence of cell-cell contact is mediated by a filamentous actin-dependent, myosin II- and phospho-YAP-independent pathway during extracellular matrix mechanosensing. J Biol Chem. 2016;291(12):6096–6110. doi:10.1074/jbc.M115.708313.
  • Rao PV, Deng PF, Kumar J, Epstein DL. Modulation of aqueous humor outflow facility by the rho kinase-specific inhibitor Y-27632. Invest Ophthalmol Vis Sci. 2001;42(5):1029–1037.
  • Wang SK, Chang RT. An emerging treatment option for glaucoma: rho kinase inhibitors. Clin Ophthalmol. 2014;8:883–890. doi:10.2147/OPTH.S41000.
  • Zhang K, Zhang L, Weinreb RN. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma. Nat Rev Drug Discov. 2012;11(7):541–559. doi:10.1038/nrd3745.

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