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Review

Advances in targeting the extracellular matrix for glaucoma therapy: current updates

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Pages 1217-1229 | Received 11 Oct 2023, Accepted 07 Dec 2023, Published online: 13 Dec 2023

References

  • Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmol. 2014;121(11):2081–2090. doi: 10.1016/j.ophtha.2014.05.013
  • Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the collaborative initial glaucoma treatment study the impact of treatment and other baseline factors. Ophthalmol. 2009;116(2):200–207. doi: 10.1016/j.ophtha.2008.08.051
  • Brubaker RF. Flow of aqueous humor in humans [the friedenwald lecture]. Invest Ophthalmol Vis Sci. 1991;32(13):3145–3166. https://iovs.arvojournals.org/article.aspx?articleid=2160397
  • Toris CB, Koepsell SA, Yablonski ME, et al. Aqueous humor dynamics in ocular hypertensive patients. J Glaucoma. 2002;11(3):253–258. doi: 10.1097/00061198-200206000-00015
  • Johnson M. What controls aqueous humour outflow resistance?. Exp Eye Res. 2006;82(4):545–557. doi: 10.1016/j.exer.2005.10.011
  • Acott TS, Vranka JA, Keller KE, et al. Normal and glaucomatous outflow regulation. Prog Retin Eye Res. 2021;82:100897. doi: 10.1016/j.preteyeres.2020.100897
  • Bradley JM, Vranka J, Colvis CM, et al. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Invest Ophthalmol Vis Sci. 1998;39(13):2649–2658. https://iovs.arvojournals.org/article.aspx?articleid=2161843
  • Gottanka J, Johnson DH, Martus P, et al. Severity of optic nerve damage in eyes with POAG is correlated with changes in the trabecular meshwork. J Glaucoma. 1997;6(2):123–132. doi: 10.1097/00061198-199704000-00009
  • 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
  • Ueda J, Wentz-Hunter K, Yue BY. Distribution of myocilin and extracellular matrix components in the juxtacanalicular tissue of human eyes. Invest Ophthalmol Vis Sci. 2002;43(4):1068–1076. https://iovs.arvojournals.org/article.aspx?articleid=2200196
  • Kasetti RB, Maddineni P, Millar JC, et al. Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork. Sci Rep. 2017;7(1):14951. doi: 10.1038/s41598-017-14938-0
  • Agarwal R, Agarwal P. Future target molecules in antiglaucoma therapy: TGF-Beta may have a role to play. Ophthalmic Res. 2010;43(1):1–10. doi: 10.1159/000246571
  • Agarwal P, Daher AM, Agarwal R. Aqueous humor TGF-β2 levels in patients with open-angle glaucoma: a meta-analysis. Mol Vis. 2015;21:612–620. http://www.molvis.org/molvis/v21/612/
  • Zhao X, Ramsey KE, Stephan DA, et al. Gene and protein expression changes in human trabecular meshwork cells treated with transforming growth factor-beta. Invest Ophthalmol Vis Sci. 2004;45(11):4023–4034. doi: 10.1167/iovs.04-0535
  • Fleenor DL, Shepard AR, Hellberg PE, et al. TGFbeta2-induced changes in human trabecular meshwork: implications for intraocular pressure. Invest Ophthalmol Vis Sci. 2006;47(1):226–234. doi: 10.1167/iovs.05-1060
  • Nakamura Y, Hirano S, Suzuki K, et al. Signaling mechanism of TGF-beta1-induced collagen contraction mediated by bovine trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2002;43(11):3465–3472. https://iovs.arvojournals.org/article.aspx?articleid=2123155
  • Hill LJ, Mead B, Thomas CN, et al. TGF-β-induced IOP elevations are mediated by RhoA in the early but not the late fibrotic phase of open angle glaucoma. Mol Vis. 2018;24:712–726. http://www.molvis.org/molvis/v24/712/
  • Sethi A, Mao W, Wordinger RJ, et al. Transforming growth factor-beta induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011;52(8):5240–5250. doi: 10.1167/iovs.11-7287
  • Welge-Lüssen U, May CA, Lütjen-Drecoll E. Induction of tissue transglutaminase in the trabecular meshwork by TGF-beta1 and TGF-beta2. Invest Ophthalmol Vis Sci. 2000;41(8):2229–2238. https://iovs.arvojournals.org/article.aspx?articleid=2123029
  • Raychaudhuri U, Millar JC, Clark AF. Tissue Transglutaminase Elevates Intraocular Pressure in Mice. Invest Ophthalmol Vis Sci. 2017;58(14):6197–6211. doi: 10.1167/iovs.17-22236
  • Cousins SW, McCabe MM, Danielpour D, et al. Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2201–2211. https://iovs.arvojournals.org/article.aspx?articleid=2160493
  • Pervan CL, Lautz JD, Blitzer AL, et al. Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells. Exp Eye Res. 2016;146:95–102. doi: 10.1016/j.exer.2015.12.010
  • Murphy-Ullrich JE, Poczatek M. Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev. 2000;11(1–2):59–69. doi: 10.1016/s1359-6101(99)00029-5
  • Kang MH, Oh DJ, Kang JH, et al. Regulation of SPARC by transforming growth factor β2 in human trabecular meshwork. Invest Ophthalmol Vis Sci. 2013;54(4):2523–2532. doi: 10.1167/iovs.12-11474
  • Haddadin RI, Oh DJ, Kang MH, et al. SPARC-null mice exhibit lower intraocular pressures. Invest Ophthalmol Vis Sci. 2009;50(8):3771–3777. doi: 10.1167/iovs.08-2489
  • Wilson SE. TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs. Exp Eye Res. 2021;207:108594. doi: 10.1016/j.exer.2021.108594
  • Junglas B, Yu AH, Welge-Lüssen U, et al. Connective tissue growth factor induces extracellular matrix deposition in human trabecular meshwork cells. Exp Eye Res. 2009;88(6):1065–1075. doi: 10.1016/j.exer.2009.01.008
  • Tovar-Vidales T, Clark AF, Wordinger RJ. Transforming growth factor-beta2 utilizes the canonical Smad-signaling pathway to regulate tissue transglutaminase expression in human trabecular meshwork cells. Exp Eye Res. 2011;93(4):442–451. doi: 10.1016/j.exer.2011.06.011
  • Finnson KW, Almadani Y, Philip A. Non-canonical (non-SMAD2/3) TGF-β signaling in fibrosis: mechanisms and targets. Semin Cell Dev Biol. 2020;101:115–122. doi: 10.1016/j.semcdb.2019.11.013
  • Pervan CL. Smad-independent TGF-β2 signaling pathways in human trabecular meshwork cells. Exp Eye Res. 2017;158:137–145. doi: 10.1016/j.exer.2016.07.012
  • Hassan MDS, Razali N, Abu Bakar AS, et al. Connective tissue growth factor: role in trabecular meshwork remodeling and intraocular pressure lowering. Exp Biol Med (Maywood). 2023;248(16):1425–1436. doi: 10.1177/15353702231199466
  • Mori S, Matsuzaki K, Yoshida K, et al. TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions. Oncogene. 2004;23(44):7416–7429. doi: 10.1038/sj.onc.1207981
  • Han H, Wecker T, Grehn F, et al. Elasticity-dependent modulation of TGF-β responses in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011;52(6):2889–2896. doi: 10.1167/iovs.10-6640
  • Peng F, Zhang B, Wu D, et al. Tgfbeta-induced RhoA activation and fibronectin production in mesangial cells require caveolae. Am J Physiol Renal Physiol. 2008;295(1):F153–F164. doi: 10.1152/ajprenal.00419.2007
  • Wang J, Liu X, Zhong Y. Rho/rho-associated kinase pathway in glaucoma. Int J Oncol. 2013;43(5):1357–1367. doi: 10.3892/ijo.2013.2100
  • Shyam R, Shen X, Yue BY, et al. Wnt gene expression in human trabecular meshwork cells. Mol Vis. 2010;16:122–9.
  • Miller JR, Hocking AM, Brown JD, et al. Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene. 1999;18(55):7860–7872. doi: 10.1038/sj.onc.1203245
  • Villarreal G Jr, Chatterjee A, Oh SS, et al. Canonical Wnt signaling regulates extracellular matrix expression in the trabecular meshwork. Invest Ophthalmol Vis Sci query. 2014;55(11):7433–7440. doi: 10.1167/iovs.13-12652
  • Dhamodaran K, Baidouri H, Sandoval L, et al. 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
  • Wang WH, McNatt LG, Pang IH, et al. Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure. J Clin Invest. 2008;118(3):1056–1064. doi: 10.1172/JCI33871
  • Sugali CK, Rayana NP, Dai J, et al. The canonical wnt signaling pathway inhibits the glucocorticoid receptor signaling pathway in the trabecular meshwork. Am J Pathol. 2021;191(6):1020–1035. doi: 10.1016/j.ajpath.2021.02.018
  • Webber HC, Bermudez JY, Sethi A, et al. Crosstalk between TGFβ and Wnt signaling pathways in the human trabecular meshwork. Exp Eye Res. 2016;148:97–102. doi: 10.1016/j.exer.2016.04.007
  • Wecker T, Han H, Börner J, et al. Effects of TGF-β2 on cadherins and β-catenin in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2013;54(10):6456–6462. doi: 10.1167/iovs.13-12669
  • Gagen D, Faralli JA, Filla MS, et al. The role of integrins in the trabecular meshwork. J Ocul Pharmacol Ther. 2014;30(2–3):110–120. doi: 10.1089/jop.2013.0176
  • Shi F, Harman J, Fujiwara K, et al. Collagen I matrix turnover is regulated by fibronectin polymerization. Am J Physiol Cell Physiol. 2010;298(5):C1265–C1275. doi: 10.1152/ajpcell.00341.2009
  • Wu C, Hughes PE, Ginsberg MH, et al. Identification of a new biological function for the integrin alpha v beta 3: initiation of fibronectin matrix assembly. Cell Adhes Commun. 1996;4(3):149–158. doi: 10.3109/15419069609014219
  • Wang D, Sun L, Zborowska E, et al. Control of type II transforming growth factor-beta receptor expression by integrin ligation. J Biol Chem. 1999;274(18):12840–12847. doi: 10.1074/jbc.274.18.12840
  • Shan SW, Do CW, Lam TC, et al. Thrombospondin-1 mediates Rho-kinase inhibitor-induced increase in outflow-facility. J Cell Physiol. 2021;236(12):8226–8238. doi: 10.1002/jcp.30492
  • Alam N, Goel HL, Zarif MJ, et al. The integrin-growth factor receptor duet. J Cell Physiol. 2007;213(3):649–653. doi: 10.1002/jcp.21278
  • Munger JS, Sheppard D. Cross talk among TGF-β signaling pathways, integrins, and the extracellular matrix. Cold Spring Harb Perspect Biol. 2011;3(11):a005017. doi: 10.1101/cshperspect.a005017
  • Taurone S, Ripandelli G, Pacella E, et al. Potential regulatory molecules in the human trabecular meshwork of patients with glaucoma: immunohistochemical profile of a number of inflammatory cytokines. Mol Med Rep. 2015;11(2):1384–1390. doi: 10.3892/mmr.2014.2772
  • Liton PB, Li G, Luna C, et al. Cross-talk between TGF-beta1 and IL-6 in human trabecular meshwork cells. Mol Vis. 2009;15:326–334.
  • Inoue-Mochita M, Inoue T, Kojima S, et al. Interleukin-6-mediated trans-signaling inhibits transforming growth factor-β signaling in trabecular meshwork cells. J Biol Chem. 2018;293(28):10975–10984. doi: 10.1074/jbc.RA118.003298
  • Liu ZW, Zhang YM, Zhang LY, et al. Duality of interactions between TGF-β and TNF-α during tumor formation. Front Immunol. 2022;12:810286. doi: 10.3389/fimmu.2021.810286
  • Alexander JP, Samples JR, Acott TS. Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression. Curr Eye Res. 1998;17(3):276–285. doi: 10.1076/ceyr.17.3.276.5219
  • Holappa M, Vapaatalo H, Vaajanen A. Many faces of Renin-angiotensin system - focus on Eye. Open Ophthalmol J. 2017;11(1):122–142. doi: 10.2174/1874364101711010122
  • Agarwal P, Agarwal R. Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target? Expert Opin Ther targets. Expert Opin Ther Targets. 2018;22(7):629–638. doi: 10.1080/14728222.2018.1486822
  • Inoue T, Yokoyoma T, Koike H. The effect of angiotensin II on uveoscleral outflow in rabbits. Curr Eye Res. 2001;23(2):139–143. doi: 10.1076/ceyr.23.2.139.5470
  • Vaajanen A, Vapaatalo H, Kautiainen H, et al. Angiotensin (1-7) reduces intraocular pressure in the normotensive rabbit eye. Invest Ophthalmol Vis Sci. 2008;49(6):2557–2562. doi: 10.1167/iovs.07-1399
  • Li H, Cui H, Ren J, et al. Elevated angiotensin-II levels contribute to the pathogenesis of open-angle glaucoma via inducing the expression of fibrosis-related genes in trabecular meshwork cells through a ROS/NOX4/SMAD3 axis. Cell Transplant. 2023;32:9636897231162526. doi: 10.1177/09636897231162526
  • Rupérez M, Lorenzo O, Blanco-Colio LM, et al. Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation. 2003;108(12):1499–1505. doi: 10.1161/01.CIR.0000089129.51288.BA
  • Choritz L, Machert M, Thieme H. Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. 2012;53(11):7336–7342. doi: 10.1167/iovs.12-10216
  • Wang J, Rong Y, Liu Y, et al. The effect of ET1-CTGF mediated pathway on the accumulation of extracellular matrix in the trabecular meshwork and its contribution to the increase in IOP. Int Ophthalmol. 2023;43(9):3297–3307. doi: 10.1007/s10792-023-02733-y
  • Song B, Zhang ZZ, Zhong JC, et al. Loss of angiotensin-converting enzyme 2 exacerbates myocardial injury via activation of the CTGF-fractalkine signaling pathway. Circ J. 2013;77(12):2997–3006. doi: 10.1253/circj.CJ-13-0805
  • Kagami S, Border WA, Miller DE, et al. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest. 1994;93(6):2431–2437. doi: 10.1172/JCI117251
  • Weigert C, Brodbeck K, Klopfer K, et al. Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemia. Diabetologia. 2002;5(6):890–898. doi: 10.1007/s00125-002-0843-4
  • Zhou Y, Poctatek MH, Berecek KH, et al. Thrombospondin 1 mediates angiotensin II induction of TGF-β activation by cardiac and renal cells under both high and low glucose conditions. Biochem Biophys Res Commun. 2006;339(2):633–641. doi: 10.1016/j.bbrc.2005.11.060
  • Wolf G, Ziyadeh FN, Stahl R. Angiotensin II stimulates expression of transforming growth factor β receptor type II in cultured mouse proximal tubular cells. J Mol Med. 1999;77(7):556–564. doi: 10.1007/s001099900028
  • De Groef L, Andries L, Siwakoti A, et al. Aberrant collagen composition of the trabecular meshwork results in reduced aqueous humor drainage and elevated IOP in MMP-9 null mice. Invest Ophthalmol Vis Sci. 2016;57(14):5984–5995. doi: 10.1167/iovs.16-19734
  • Määttä M, Tervahartiala T, Harju M, et al. Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma. J Glaucoma. 2005;14(1):64–69. doi: 10.1097/01.ijg.0000145812.39224.0a
  • Razali N, Agarwal R, Agarwal P, et al. Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs. Eur J Pharmacol. 2015;749:73–80. doi: 10.1016/j.ejphar.2014.11.029
  • Razali N, Agarwal R, Agarwal P, et al. Topical trans-resveratrol ameliorates steroid-induced anterior and posterior segment changes in rats. Exp Eye Res. 2016;143:9–16. doi: 10.1016/j.exer.2015.09.014
  • Gindina S, Hu Y, Barron AO, et al. Tissue plasminogen activator attenuates outflow facility reduction in mouse model of juvenile open angle glaucoma. Exp Eye Res. 2020;199:108179. doi: 10.1016/j.exer.2020.108179
  • Zhao Y, Lyons CE Jr, Xiao A, et al. Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochemical And Biophysical Research Communications. 2008;369(4):1215–1220. doi: 10.1016/j.bbrc.2008.03.038
  • Kohler HP, Grant PJ, Epstein FH. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 2000;342(24):1792–1801. doi: 10.1056/NEJM200006153422406
  • Dan J, Belyea D, Gertner G, et al. Plasminogen activator inhibitor-1 in the aqueous humor of patients with and without glaucoma. Arch Ophthalmol. 2005;123(2):220–224. doi: 10.1001/archopht.123.2.220
  • Zhong S, Khalil RA. A disintegrin and metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS) family in vascular biology and disease. Biochem Pharmacol. 2019;164:188–204. doi: 10.1016/j.bcp.2019.03.033
  • Keller KE, Bradley JM, Acott TS. Differential effects of ADAMTS-1, -4, and -5 in the trabecular meshwork. Invest Ophthalmol Vis Sci. 2009;50(12):5769–5777. doi: 10.1167/iovs.09-3673
  • Wordinger RJ, Agarwal R, Talati M, et al. Expression of bone morphogenetic proteins (BMP), BMP receptors, and BMP associated proteins in human trabecular meshwork and optic nerve head cells and tissues. Mol Vis. 2002;8:241–250. http://www.molvis.org/molvis/v8/a31/
  • Fuchshofer R, Stephan DA, Russell P, et al. Gene expression profiling of TGFbeta2- and/or BMP7-treated trabecular meshwork cells: identification of Smad7 as a critical inhibitor of TGF-beta2 signaling. Exp Eye Res. 2009;88(6):1020–1032. doi: 10.1016/j.exer.2009.01.002
  • Wordinger RJ, Sharma T, Clark AF. The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. J Ocul Pharmacol Ther. 2014;30(2–3):154–162. doi: 10.1089/jop.2013.0220
  • Shimasaki S, Moore RK, Otsuka F, et al. The bone morphogenetic protein system in mammalian reproduction. Endocr Rev. 2004;25(1):72–101. doi: 10.1210/er.2003-0007
  • Sethi A, Wordinger RJ, Clark AF. Gremlin utilizes canonical and non-canonical TGFβ signaling to induce lysyl oxidase (LOX) genes in human trabecular meshwork cells. Exp Eye Res. 2013;113:117–127. doi: 10.1016/j.exer.2013.05.011
  • Hernandez H, Millar JC, Curry SM, et al. BMP and activin membrane bound inhibitor regulates the extracellular matrix in the trabecular meshwork. Invest Ophthalmol Vis Sci. 2018;59(5):2154–2166. doi: 10.1167/iovs.17-23282
  • Yan X, Lin Z, Chen F, et al. Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling. J Biol Chem. 2009;284(44):30097–30104. doi: 10.1074/jbc.M109.049304
  • Mzyk P, Hernandez H, Le T, et al. Toll-like receptor 4 signaling in the trabecular meshwork. Front Cell Dev Biol. 2022;10:936115. doi: 10.3389/fcell.2022.936115
  • McKeown-Longo PJ, Higgins PJ. Integration of canonical and noncanonical pathways in TLR4 signaling: complex regulation of the wound repair program. Adv Wound Care (New Rochelle). 2017;6(10):320–329. doi: 10.1089/wound.2017.0736
  • Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998;273(22):13375–13378. doi: 10.1074/jbc.273.22.13375
  • Trojanowska M. Noncanonical transforming growth factor beta signaling in scleroderma fibrosis. Curr Opin Rheumatol. 2009;21(6):623–629. doi: 10.1097/BOR.0b013e32833038ce
  • Tellios N, Belrose JC, Tokarewicz AC, et al. TGF-β induces phosphorylation of phosphatase and tensin homolog: implications for fibrosis of the trabecular meshwork tissue in glaucoma. Sci Rep. 2017;7(1):812. doi: 10.1038/s41598-017-00845-x
  • Igarashi N, Honjo M, Aihara M. mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells. Sci Rep. 2021;11(1):14111. doi: 10.1038/s41598-021-93580-3
  • Mead AL, Wong TT, Cordeiro MF, et al. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest Ophthalmol Vis Sci. 2003;44(8):3394–33401. doi: 10.1167/iovs.02-0978
  • CAT-152 0102 Trabeculectomy Study Group, Khaw P, Grehn F, et al. A phase III study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmol. 2007;114(10):1822–1830. doi: 10.1016/j.ophtha.2007.03.050
  • Teplitsky JE, Vinokurtseva A, Armstrong JJ, et al. ALK5 inhibition of subconjunctival scarring from glaucoma surgery: effects of SB-431542 compared to mitomycin C in human tenon’s capsule fibroblasts. Transl Vis Sci Technol. 2023;12(2):31. doi: 10.1167/tvst.12.2.31
  • Pfeiffer N, Voykov B, Renieri G, et al. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery. PLoS One. 2017;12(11):e0188899. doi: 10.1371/journal.pone.0188899
  • Oshitari T, Wang N, Li AF, et al. Excess fibronectin accumulation in the trabecular meshwork: a potential mechanism for increasing aqueous outflow resistance. Invest Ophthalmol Vis Sci. 2006;47(13):1837–1837. https://iovs.arvojournals.org/article.aspx?articleid=2391694
  • Luna C, Li G, Qiu J, et al. Cross-talk between miR-29 and transforming growth factor-betas in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2011;52(6):3567–3572. doi: 10.1167/iovs.10-6448
  • Stahnke T, Kowtharapu BS, Stachs O, et al. Suppression of TGF-β pathway by pirfenidone decreases extracellular matrix deposition in ocular fibroblasts in vitro. PLoS One. 2017;12(2):e0172592. doi: 10.1371/journal.pone.0172592
  • Knox J, Bou-Gharios G, Hamill KJ, et al. MiR-18a-5p targets connective tissue growth factor expression and inhibits transforming growth factor beta2-induced trabecular meshwork cell contractility. Genes. 2022;13(8):1500–1513. doi: 10.3390/genes13081500
  • Guo JH, Su C, Jiang SY, et al. MicroRNA-1 regulates fibronectin expression in human trabecular meshwork cells under oxidative stress. Zhonghua Yan Ke Za Zhi. 2019;55(5):355–360. doi: 10.3760/cma.j.issn.0412-4081.2019.05.009
  • Luna C, Li G, Qiu J, et al. MicroRNA-24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN. J Cell Physiol. 2011;226(5):1407–1414. doi: 10.1002/jcp.22476
  • Buffault J, Brignole-Baudouin F, Reboussin É, et al. The dual effect of Rho-kinase inhibition on trabecular meshwork cells cytoskeleton and extracellular matrix in an in vitro model of glaucoma. J Clin Med. 2022;11(4):1001. doi: 10.3390/jcm11041001
  • Peterson JA, Tian B, Bershadsky AD, et al. Latrunculin-A increases outflow facility in the monkey. Invest Ophthalmol Vis Sci. 1999;40(5):931–941. https://iovs.arvojournals.org/article.aspx?articleid=2162035
  • Peterson JA, Tian B, Geiger B, et al. Effect of latrunculin-B on outflow facility in monkeys. Exp Eye Res. 2000;70(3):307–313. doi: 10.1006/exer.1999.0797
  • Ha A, Kim YK, Jeoung JW, et al. Sovesudil (locally acting rho kinase inhibitor) for the treatment of normal-tension glaucoma: the randomized phase II study. Acta Ophthalmol. 2022;100(2):e470–e477. doi: 10.1111/aos.14949
  • Song J, Deng PF, Stinnett SS, et al. 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
  • Sun Y, Li Y, Wang H, et al. miR-146a-5p acts as a negative regulator of TGF-β signaling in skeletal muscle after acute contusion. Acta Biochim Biophys Sin (Shanghai). 2017;49(7):628–634. doi: 10.1093/abbs/gmx052
  • Luna C, Parker M, Challa P, et al. Long-term decrease of intraocular pressure in rats by viral delivery of miR-146a. Transl Vis Sci Technol. 2021 Jul 1;10(8):14. doi: 10.1167/tvst.10.8.14
  • Inoue-Mochita M, Inoue T, Fujimoto T, et al. p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells. PLoS One. 2015;10(3):e0120774. doi: 10.1371/journal.pone.0120774
  • Huang L, Wei Z, Wang X, et al. AZD6738 decreases intraocular pressure and inhibits fibrotic response in trabecular meshwork through CHK1/P53 pathway. Biochem Pharmacol. 2022;206:115340. doi: 10.1016/j.bcp.2022.115340
  • Mzyk P, Zalog EG, McDowell CM. A20 attenuates the fibrotic response in the trabecular meshwork. Int J Mol Sci. 2022;23(4):1928. doi: 10.3390/ijms23041928
  • Fujimoto T, Inoue-Mochita M, Iraha S, et al. Suberoylanilide hydroxamic acid (SAHA) inhibits transforming growth factor-beta 2-induced increases in aqueous humor outflow resistance. J Biol Chem. 2021;297(3):101070. doi: 10.1016/j.jbc.2021.101070
  • Shah GB, Sharma S, Mehta AA, et al. Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and chronic models of glaucoma. J Cardiovasc Pharmacol. 2000;36(2):169–175. doi: 10.1097/00005344-200008000-00005
  • Constad WH, Fiore P, Samson C, et al. Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open-angle glaucoma. Am J Ophthalmol. 1988;105(6):674–677. doi: 10.1016/0002-9394(88)90063-3
  • Agarwal R, Krasilnikova AV, Raja IS, et al. Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in normotensive rats. Eur J Pharmacol. 2014;730:8–13. doi: 10.1016/j.ejphar.2014.02.021
  • Agarwal R, Krasilnikova AV, Mohamed SNL, et al. Topical losartan reduces IOP by altering tm morphology in rats with steroid-induced ocular hypertension. Ind J Physiol Pharmacol. 2018;62(2):238–248.
  • Khawaja AP, Chan MP, Broadway DC, et al. Systemic medication and intraocular pressure in a British population: the EPIC-Norfolk Eye study. Ophthalmol. 2014;121(8):1501–1507. doi: 10.1016/j.ophtha.2014.02.009
  • Luna C, Li G, Huang J, et al. Regulation of trabecular meshwork cell contraction and intraocular pressure by miR-200c. PLoS One. 2012;7(12):e51688. doi: 10.1371/journal.pone.0051688
  • Brubaker RF. Mechanism of action of bimatoprost (Lumigan). Surv Ophthalmol. 2001;45 Suppl 4:S347–S351. doi: 10.1016/s0039-6257(01)00213-2
  • Lindsey JD, Kashiwagi K, Boyle D, et al. Prostaglandins increase proMMP-1 and proMMP-3 secretion by human ciliary smooth muscle cells. Curr Eye Res. 1996;15(8):869–875. doi: 10.3109/02713689609017628
  • Weinreb RN, Robinson MR, Dibas M, et al. Matrix Metalloproteinases and Glaucoma Treatment. J Ocul Pharmacol Ther. 2020;36(4):208–228. doi: 10.1089/jop.2019.0146
  • Morozumi W, Aoshima K, Inagaki S, et al. Piezo1 activation induces fibronectin reduction and PGF2α secretion via arachidonic acid cascade. Exp Eye Res. 2022;215:108917. doi: 10.1016/j.exer.2021.108917
  • Nakamura N, Honjo M, Yamagishi R, et al. Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction. Sci Rep. 2021;11(1):16257. doi: 10.1038/s41598-021-95768-z
  • Razali N, Agarwal R, Agarwal P, et al. IOP lowering effect of topical trans-resveratrol involves adenosine receptors and TGF-β2 signaling pathways. Eur J Pharmacol. 2018;838:1–10. doi: 10.1016/j.ejphar.2018.08.035
  • Mohd Nasir NA, Agarwal R, Krasilnikova A, et al. Effect of trans-resveratrol on dexamethasone-induced changes in the expression of MMPs by human trabecular meshwork cells: involvement of adenosine A1 receptors and NFkB. Eur J Pharmacol. 2020;887:173431. doi: 10.1016/j.ejphar.2020.173431
  • Li G, Torrejon KY, Unser AM, et al. Trabodenoson, an adenosine mimetic with A1 receptor selectivity lowers intraocular pressure by increasing conventional outflow facility in mice. Invest Ophthalmol Vis Sci. 2018;59(1):383–392. doi: 10.1167/iovs.17-23212
  • Husain S, Shearer TW, Crosson CE. Mechanisms linking adenosine A1 receptors and extracellular signal-regulated kinase 1/2 activation in human trabecular meshwork cells. J Pharmacol Exp Ther. 2007;320(1):258–265. doi: 10.1124/jpet.106.110981
  • Hill LJ, Mead B, Blanch RJ, et al. Decorin reduces intraocular pressure and retinal ganglion cell loss in rodents through fibrolysis of the scarred trabecular meshwork. Invest Ophthalmol Vis Sci. 2015;56(6):3743–3757. doi: 10.1167/iovs.14-15622

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