The role of TGF-β in the pathogenesis of primary open-angle glaucoma

Cell and Tissue Research

Volumn 347, Issue 1, 2012, Pages 279-290

  Fuchshofer, Rudolf ^a   Tamm, Ernst R ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

Author keywords

Astrocytes; Extracellular matrix; Glaucoma; Growth factors; Optic nerve; Trabecular meshwork

Indexed keywords

BONE MORPHOGENETIC PROTEIN 4; CONNECTIVE TISSUE GROWTH FACTOR; GLYCOPROTEIN; GREMLIN PROTEIN; MICRORNA; OSTEOGENIC PROTEIN 1; PLASMINOGEN ACTIVATOR INHIBITOR 1; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; UNCLASSIFIED DRUG;

ACTIN FILAMENT; AQUEOUS HUMOR OUTFLOW; CELL METABOLISM; EXTRACELLULAR MATRIX; GENE OVEREXPRESSION; HUMAN; IMMUNOREACTIVITY; INTRAOCULAR PRESSURE ABNORMALITY; MECHANICAL STRESS; NERVE CELL DEGENERATION; NERVE FIBER TRANSPORT; NONHUMAN; OPEN ANGLE GLAUCOMA; OPTIC NERVE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; REVIEW; RNA INTERFERENCE; STRESS STRAIN RELATIONSHIP; TRABECULAR MESHWORK;

ACTIN CYTOSKELETON; ANIMALS; DISEASE MODELS, ANIMAL; EXTRACELLULAR MATRIX; GLAUCOMA, OPEN-ANGLE; HUMANS; INTRAOCULAR PRESSURE; OPTIC DISK; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA2;

EID: 84859441225     PISSN: 0302766X     EISSN: 14320878     Source Type: Journal    
DOI: 10.1007/s00441-011-1274-7     Document Type: Review

References (179)

1. Adams JC (2001) Thrombospondins: multifunctional regulators of cell interactions. Annu Rev Cell Dev Biol 17:25-51
2. Allen JB, Davidson MG, Nasisse MP, Fleisher LN, McGahan MC (1998) The lens influences aqueous humor levels of transforming growth factor-beta 2. Graefes Arch Clin Exp Ophthalmol 236:305-311 (Pubitemid 28152217)
3. Alm A, Nilsson SF (2009) Uveoscleral outflow - a review. Exp Eye Res 88:760-768
4. Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGFßactivation. J Cell Sci 116:217-224
5. Attisano L, Wrana JL (2002) Signal transduction by the TGF-beta superfamily. Science 296:1646-1647
6. Bachmann B, Birke M, Kook D, Eichhorn M, Lütjen-Drecoll E (2006) Ultrastructural and biochemical evaluation of the porcine anterior chamber perfusion model. Invest Ophthalmol Vis Sci 47:2011-2020 (Pubitemid 46768283)
7. Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209-218 (Pubitemid 40385459)
8. Bhattacharya SK, Rockwood EJ, Smith SD, Bonilha VL, Crabb JS, Kuchtey RW, Robertson NG, Peachey NS, Morton CC, Crabb JW (2005) Proteomics reveal cochlin deposits associated with glaucomatous trabecular meshwork. J Biol Chem 280:6080-6084 (Pubitemid 40280092)
9. Bhattacharya SK, Gabelt BT, Ruiz J, Picciani R, Kaufman PL (2009) Cochlin expression in anterior segment organ culture models after TGFbeta2 treatment. Invest Ophthalmol Vis Sci 50:551-559
10. Bollinger KE, Crabb JS, Yuan X, Putliwala T, Clark AF, Crabb JW (2011) Quantitative proteomics: TGF{beta}2-signaling in trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:8287-8294
11. Bornstein P (2001) Thrombospondins as matricellular modulators of cell function. J Clin Invest 107:929-934
12. Bradley JM, Vranka J, Colvis CM, Conger DM, Alexander JP, Fisk AS, Samples JR, Acott TS (1998) Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Invest Ophthalmol Vis Sci 39:2649-2658 (Pubitemid 28558223)
13. Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A (2011) Bone morphogenetic proteins: a critical review. Cell Signal 23:609-620
14. Brubaker RF (1991) Flow of aqueous humor in humans (the Friedenwald Lecture). Invest Ophthalmol Vis Sci 32:3145-3166
15. Burgoyne CF (2011) A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma. Exp Eye Res 93:120-132
16. Chand HS, Foster DC, Kisiel W (2005) Structure, function and biology of tissue factor pathway inhibitor-2. Thromb Haemost 94:1122-1130 (Pubitemid 41819605)
17. Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233-241 (Pubitemid 40136452)
18. Chen J, Li H, SundarRaj N, Wang JH (2007) Alpha-smooth muscle actin expression enhances cell traction force. Cell Motil Cytoskeleton 64:248-257 (Pubitemid 46452034)
19. Clark AF, Wordinger RJ (2009) The role of steroids in outflow resistance. Exp Eye Res 88:752-759
20. Clark AF, Wilson K, McCartney MD, Miggans ST, Kunkle M, Howe W (1994) Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci 35:281-294 (Pubitemid 24046852)
21. Clark AF, Miggans ST, Wilson K, Browder S, McCartney MD (1995) Cytoskeletal changes in cultured human glaucoma trabecular meshwork cells. J Glaucoma 4:183-188
22. Clark AF, Brotchie D, Read AT, Hellberg P, English-Wright S, Pang IH, Ethier CR, Grierson I (2005) Dexamethasone alters F-actin architecture and promotes cross-linked actin network formation in human trabecular meshwork tissue. Cell Motil Cytoskeleton 60:83-95 (Pubitemid 40165322)
23. Collaborative Normal-Tension Glaucoma Study Group (1998a) Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 126:487-497
24. Collaborative Normal-Tension Glaucoma Study Group (1998b) The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 126:498-505
25. Cousins SW, McCabe MM, Danielpour D, Streilein JW (1991) Identification of transforming growth factor-beta as an immunosuppresive factor in aqueous humor. Invest Ophthalmol Vis Sci 32:2201-2211
26. Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N (1998) Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell 93:1159-1170 (Pubitemid 28307421)
27. Dan J, Belyea D, Gertner G, Leshem I, Lusky M, Miskin R (2005) Plasminogen activator inhibitor-1 in the aqueous humor of patients with and without glaucoma. Arch Ophthalmol 123:220-224 (Pubitemid 40189710)
28. Derhaschnig U, Shehata M, Herkner H, Bur A, Woisetschlager C, Laggner AN, Hirschl MM (2002) Increased levels of transforming growth factor-beta1 in essential hypertension. Am J Hypertens 15:207-211 (Pubitemid 34226183)
29. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103-111 (Pubitemid 23188802)
30. Dijke P ten, Hill CS (2004) New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29:265-273
31. Filla MS, Woods A, Kaufman PL, Peters DM (2006) Beta1 and beta3 integrins cooperate to induce syndecan-4-containing cross-linked actin networks in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 47:1956-1967 (Pubitemid 46768276)
32. Filla MS, Schwinn MK, Nosie AK, Clark RW, Peters DM (2011) Dexamethasone-associated cross-linked actin network formation in human trabecular meshwork cells involves beta3 integrin signaling. Invest Ophthalmol Vis Sci 52:2952-2959
33. Fleenor DL, Shepard AR, Hellberg PE, Jacobson N, Pang IH, Clark AF (2006) TGFbeta2-induced changes in human trabecular meshwork: implications for intraocular pressure. Invest Ophthalmol Vis Sci 47:226-234 (Pubitemid 46780818)
34. Flügel C, Tamm E, Lütjen-Drecoll E, Stefani FH (1992) Age-related loss of α-smooth muscle actin in normal and glaucomatous human trabecular meshwork of different age groups. J Glaucoma 1:165-173
35. Flügel-Koch C, Ohlmann A, Piatigorsky J, Tamm ER (2002) Disruption of anterior segment development by TGF-beta1 overexpression in the eyes of transgenic mice. Dev Dyn 225:111-125
36. Flügel-Koch C, Ohlmann A, Fuchshofer R, Welge-Lüssen U, Tamm ER (2004) Thrombospondin-1 in the trabecular meshwork: localization in normal and glaucomatous eyes, and induction by TGF-beta1 and dexamethasone in vitro. Exp Eye Res 79:649-663 (Pubitemid 39410368)
37. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ (2002) The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 86:238-242 (Pubitemid 34127552)
38. Fuchshofer R, Tamm ER (2009) Modulation of extracellular matrix turnover in the trabecular meshwork. Exp Eye Res 88:683-688
39. Fuchshofer R, Welge-Lüssen U, Lütjen-Drecoll E (2003) The effect of TGF-beta2 on human trabecular meshwork extracellular proteolytic system. Exp Eye Res 77:757-765 (Pubitemid 37373590)
40. Fuchshofer R, Birke M, Welge-Lüssen U, Kook D, Lütjen-Drecoll E (2005) Transforming growth factor-beta 2 modulated extracellular matrix component expression in cultured human optic nerve head astrocytes. Invest Ophthalmol Vis Sci 46:568-578 (Pubitemid 40270337)
41. Fuchshofer R, Yu AH, Welge-Lüssen U, Tamm ER (2007) Bone morphogenetic protein-7 is an antagonist of transforming growth factor-beta2 in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 48:715-726 (Pubitemid 351260705)
42. Fuchshofer R, Stephan DA, Russell P, Tamm ER (2009) 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 88:1020-1032
43. Gamulescu MA, Chen Y, He S, Spee C, Jin M, Ryan SJ, Hinton DR (2006) Transforming growth factor beta2-induced myofibroblastic differentiation of human retinal pigment epithelial cells: regulation by extracellular matrix proteins and hepatocyte growth factor. Exp Eye Res 83:212-222 (Pubitemid 43783243)
44. Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Kass MA (2002) The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 120:714-720 (Pubitemid 34620349)
45. Gordon WE 3rd, Bushnell A (1979) Immunofluorescent and ultrastructural studies of polygonal microfilament networks in respreading non-muscle cells. Exp Cell Res 120:335-348
46. Gordon-Thomson C, Iongh RU de, Hales AM, Chamberlain CG, McAvoy JW (1998) Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their expression in the postnatal rat eye. Invest Ophthalmol Vis Sci 39:1399-1409 (Pubitemid 28307365)
47. Gottanka J, Chan D, Eichhorn M, Lütjen-Drecoll E, Ethier CR (2004) Effects of TGF-β2 in perfused human eyes. Invest Ophthalmol Vis Sci 45:153-158 (Pubitemid 38055681)
48. Gottanka J, Kuhlmann A, Scholz M, Johnson DH, Lutjen-Drecoll E (2005) Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci 46:4170-4181 (Pubitemid 44264620)
49. Granstein RD, Staszewski R, Knisley TL, Zeira E, Nazareno R, Latina M, Albert DM (1990) Aqueous humor contains transforming growth factor-β and a small (<3500 Daltons) inhibitor of thymocyte proliferation. J Immunol 144:3021-3027 (Pubitemid 20149474)
50. Grant WM (1951) Clinical measurements of aqueous outflow. AMA Arch Ophthalmol 46:113-131
51. Grant WM (1963) Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol 69:783-801
52. Gressner AM, Weiskirchen R (2006) Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med 10:76-99 (Pubitemid 44874293)
53. Hales AM, Chamberlain CG, McAvoy JW (2000) Susceptibility to TGFbeta2-induced cataract increases with aging in the rat. Invest Ophthalmol Vis Sci 41:3544-3551
54. Han H, Wecker T, Grehn F, Schlunck G (2011) Elasticity-dependent modulation of TGF-beta responses in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:2889-2896
55. Helbig H, Kittredge KL, Coca-Prados M, Davis J, Palestine AG, Nussenblatt RB (1991) Mammalian ciliary-body epithelial cells in culture produce transforming growth factor-beta. Graefes Arch Clin Exp Ophthalmol 229:84-87
56. Hernandez MR (2000) The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res 19:297-321
57. Hernandez MR, Pena JD (1997) The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol 115:389-395
58. Hernandez MR, Igoe F, Neufeld AH (1988) Cell culture of the human lamina cribrosa. Invest Ophthalmol Vis Sci 29:78-89 (Pubitemid 18038774)
59. Hernandez MR, Andrzejewska WM, Neufeld AH (1990) Changes in the extracellular matrix of the human optic nerve head in primary open-angle glaucoma. Am J Ophthalmol 109:180-188 (Pubitemid 20048416)
60. Hernandez MR, Ye H, Roy S (1994) Collagen type IV gene expression in human optic nerve heads with primary open angle glaucoma. Exp Eye Res 59:41-51 (Pubitemid 24257143)
61. Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C (2001) Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell 12:2730-2741 (Pubitemid 33051938)
62. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807-1816 (Pubitemid 47339255)
63. Hoare MJ, Grierson I, Brotchie D, Pollock N, Cracknell K, Clark AF (2009) Cross-linked actin networks (CLANs) in the trabecular meshwork of the normal and glaucomatous human eye in situ. Invest Ophthalmol Vis Sci 50:1255-1263
64. Huggins JT, Sahn SA (2004) Causes and management of pleural fibrosis. Respirology 9:441-447 (Pubitemid 40179748)
65. Ihn H (2002a) The role of TGF-beta signaling in the pathogenesis of fibrosis in scleroderma. Arch Immunol Ther Exp (Warsz) 50:325-331
66. Ihn H (2002b) Pathogenesis of fibrosis: role of TGF-β and CTGF. Curr Opin Rheumatol 14:681-685
67. Inatani M, Tanihara H, Katsuta H, Honjo M, Kido N, Honda Y (2001) Transforming growth factor-β2 levels in aqueous humor of glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol 239:109-113 (Pubitemid 32288460)
68. Itoh S, Dijke P ten (2007) Negative regulation of TGF-beta receptor/Smad signal transduction. Curr Opin Cell Biol 19:176-184 (Pubitemid 46386411)
69. Jampel HD, Roche N, Stark WJ, Roberts AB (1990) Transforming growth factor-β in human aqueous humor. Curr Eye Res 9:963-969 (Pubitemid 20372121)
70. Jester JV, Barry-Lane PA, Cavanagh HD, Petroll WM (1996) Induction of alpha-smooth muscle actin expression and myofibroblast transformation in cultured corneal keratocytes. Cornea 15:505-516 (Pubitemid 26271790)
71. Johnson DH, Tschumper RC (1989) The effect of organ culture on human trabecular meshwork. Exp Eye Res 49:113-127 (Pubitemid 19190157)
72. Johnson M (2006) What controls aqueous humour outflow resistance? Exp Eye Res 82:545-557
73. Johnson M, Erickson K (2000) Mechanisms and routes of aqueous humor drainage. In: Albert DM, Jakobiec FA (eds) Principles and practice of ophthalmology. Saunders, Philadelphia, pp 2577-2595
74. Johnson M, Chan D, Read AT, Christensen C, Sit A, Ethier CR (2002) The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes. Invest Ophthalmol Vis Sci 43:2950-2955 (Pubitemid 34977044)
75. Junglas B, Yu AH, Welge-Lussen U, Tamm ER, Fuchshofer R (2009) Connective tissue growth factor induces extracellular matrix deposition in human trabecular meshwork cells. Exp Eye Res 88:1065-1075
76. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO (2002) The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 120:701-713 (Pubitemid 34620348)
77. Kater AW de, Shahsafaei A, Epstein DL (1992) Localization of smooth muscle and nonmuscle actin isoforms in the human aqueous outflow pathway. Invest Ophthalmol Vis Sci 33:424-429
78. Kirwan RP, Crean JK, Fenerty CH, Clark AF, O'Brien CJ (2004) Effect of cyclical mechanical stretch and exogenous transforming growth factor-beta1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head. J Glaucoma 13:327-334 (Pubitemid 38944202)
79. Kirwan RP, Leonard MO, Murphy M, Clark AF, O'Brien CJ (2005) Transforming growth factor-beta-regulated gene transcription and protein expression in human GFAP-negative lamina cribrosa cells. Glia 52:309-324 (Pubitemid 43076223)
80. Kirwan RP, Wordinger RJ, Clark AF, O'Brien CJ (2009) Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human lamina cribrosa cells. Mol Vis 15:76-88
81. Küchle M, Vinores SA, Mahlow J, Green WR (1996) Blood-aqueous barrier in pseudoexfoliation syndrome: evaluation by immunohistochemical staining of endogenous albumin. Graefes Arch Clin Exp Ophthalmol 234:12-18
82. Kusakabe M, Cheong PL, Nikfar R, McLennan IS, Koishi K (2008) The structure of the TGF-beta latency associated peptide region determines the ability of the proprotein convertase furin to cleave TGF-betas. J Cell Biochem 103:311-320
83. Kwon YH, Fingert JH, Kuehn MH, Alward WL (2009) Primary open-angle glaucoma. N Engl J Med 360:1113-1124
84. Lamouille S, Derynck R (2010) Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-beta-induced epithelial-mesenchymal transition. Cells Tissues Organs 193:8-22
85. Last JA, Pan T, Ding Y, Reilly CM, Keller K, Acott TS, Fautsch MP, Murphy CJ, Russell P (2011) Elastic modulus determination of normal and glaucomatous human trabecular meshwork. Invest Ophthalmol Vis Sci 52:2147-2152
86. Lazarides E (1976) Actin, alpha-actinin, and tropomyosin interaction in the structural organization of actin filaments in nonmuscle cells. J Cell Biol 68:202-219
87. Lepple-Wienhues A, Stahl F, Wiederholt M (1991) Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle. Exp Eye Res 53:33-38
88. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E (2003) Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol 121:48-56 (Pubitemid 36401765)
89. Li J, Tripathi BJ, Tripathi RC (2000) Modulation of pre-mRNA splicing and protein production of fibronectin by TGF-β2 in porcine trabecular cells. Invest Ophthalmol Vis Sci 41:3437-3443
90. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP (2001) Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology 108:1943-1953
91. Liton PB, Liu X, Challa P, Epstein DL, Gonzalez P (2005) Induction of TGF-beta1 in the trabecular meshwork under cyclic mechanical stress. J Cell Physiol 205:364-371 (Pubitemid 41598850)
92. Liu Y (2006) Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 69:213-217
93. Luna C, Li G, Qiu J, Epstein DL, Gonzalez P (2011a) MicroRNA-24 regulates the processing of latent TGFbeta1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN. J Cell Physiol 226:1407-1414
94. Luna C, Li G, Qiu J, Epstein DL, Gonzalez P (2011b) Cross-talk between miR-29 and transforming growth factor-betas in trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:3567-3572
95. Lütjen-Drecoll E (2005) Morphological changes in glaucomatous eyes and the role of TGFbeta2 for the pathogenesis of the disease. Exp Eye Res 81:1-4
96. Lütjen-Drecoll E, Shimizu T, Rohrbach M, Rohen JW (1986) Quantitative analysis of "plaque material" in the inner and outer wall of Schlemm's canal in normal and glaucomatous eyes. Exp Eye Res 42:443-455 (Pubitemid 16121084)
97. Margadant C, Sonnenberg A (2010) Integrin-TGF-beta crosstalk in fibrosis, cancer and wound healing. EMBO Rep 11:97-105
98. Min SH, Lee TI, Chung YS, Kim HK (2006) Transforming growth factor-beta levels in human aqueous humor of glaucomatous, diabetic and uveitic eyes. Korean J Ophthalmol 20:162-165
99. Miyazono K, Kamiya Y, Morikawa M (2010) Bone morphogenetic protein receptors and signal transduction. J Biochem 147:35-51
100. Murphy-Ullrich JE, Poczatek M (2000) Activation of latent TGF-β by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev 11:59-69 (Pubitemid 30169726)
101. Nakamura Y, Hirano S, Suzuki K, Seki K, Sagara T, Nishida T (2002) Signaling mechanism of TGF-beta1-induced collagen contraction mediated by bovine trabecular meshwork cells. Invest Ophthalmol Vis Sci 43:3465-3472 (Pubitemid 35334354)
102. Neufeld AH, Liu B (2003) Glaucomatous optic neuropathy: when glia misbehave. Neuroscientist 9:485-495 (Pubitemid 37467361)
103. Neufeld AH, Hernandez MR, Gonzalez M (1997) Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol 115:497-503 (Pubitemid 27172706)
104. Neumann C, Yu A, Welge-Lussen U, Lutjen-Drecoll E, Birke M (2008) The effect of TGF-beta2 on elastin, type VI collagen, and components of the proteolytic degradation system in human optic nerve astrocytes. Invest Ophthalmol Vis Sci 49:1464-1472
105. Nishimura SL (2009) Integrin-mediated transforming growth factor-beta activation, a potential therapeutic target in fibrogenic disorders. Am J Pathol 175:1362-1370
106. Ochiai Y, Ochiai H (2002) Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes. Jpn J Ophthalmol 46:249-253 (Pubitemid 34626632)
107. Ohji M, Sundarraj N, Thoft RA (1993) Transforming growth factor-beta stimulates collagen and fibronectin synthesis by human corneal stromal fibroblasts in vitro. Curr Eye Res 12:703-709 (Pubitemid 23267150)
108. O'Reilly S, Pollock N, Currie L, Paraoan L, Clark AF, Grierson I (2011) Inducers of cross-linked actin networks (CLANs) in trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:7316-7324
109. Overby DR, Stamer WD, Johnson M (2009) The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium. Exp Eye Res 88:656-670
110. Ozcan AA, Ozdemir N, Canataroglu A (2004) The aqueous levels of TGF-beta2 in patients with glaucoma. Int Ophthalmol 25:19-22 (Pubitemid 38443407)
111. Park SH (2005) Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads. J Biochem Mol Biol 38:9-16
112. Pasquale LR, Dorman-Pease ME, Lutty GA, Quigley HA, Jampel HD (1993) Immunolocalization of TGF-β1, TGF-β2, and TGF-β3 in the anterior segment of the human eye. Invest Ophthalmol Vis Sci 34:23-30 (Pubitemid 23045098)
113. Pattabiraman PP, Rao PV (2010) Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol 298:C749-C763
114. Pena JD, Roy S, Hernandez MR (1996) Tropoelastin gene expression in optic nerve heads of normal and glaucomatous subjects. Matrix Biol 15:323-330 (Pubitemid 26419877)
115. Pena JD, Netland PA, Vidal I, Dorr DA, Rasky A, Hernandez MR (1998) Elastosis of the lamina cribrosa in glaucomatous optic neuropathy. Exp Eye Res 67:517-524 (Pubitemid 29005148)
116. Pena JD, Taylor AW, Ricard CS, Vidal I, Hernandez MR (1999) Transforming growth factor beta isoforms in human optic nerve heads. Br J Ophthalmol 83:209-218 (Pubitemid 29106092)
117. Pfeffer BA, Flanders KC, Guerin CJ, Danielpour D, Anderson DH (1994) Transforming growth factor beta 2 is the predominant isoform in the neural retina, retinal pigment epithelium-choroid and vitreous of the monkey eye. Exp Eye Res 59:323-333 (Pubitemid 24326996)
118. Phanish MK, Winn SK, Dockrell ME (2009) Connective tissue growth factor-(CTGF, CCN2)-a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol 114:e83-e92
119. Picht G, Welge-Luessen U, Grehn F, Lütjen-Drecoll E (2001) Transforming growth factor-β2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development. Graefes Arch Clin Exp Ophthalmol 239:199-207 (Pubitemid 32422026)
120. Quigley HA (1999) Neuronal death in glaucoma. Prog Retin Eye Res 18:39-57
121. Quigley HA (2011) Glaucoma. Lancet 377:1367-1377
122. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR (1983) Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol 95:673-691 (Pubitemid 13092793)
123. Read AT, Chan DW, Ethier CR (2006) Actin structure in the outflow tract of normal and glaucomatous eyes. Exp Eye Res 82:974-985
124. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82:844-851 (Pubitemid 39573742)
125. Ritch R, Schlötzer-Schrehardt U, Konstas AG (2003) Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res 22:253-275 (Pubitemid 38401056)
126. Robertson JV, Golesic E, Gauldie J, West-Mays JA (2010) Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats. Invest Ophthalmol Vis Sci 51:308-318
127. Rohen JW, Witmer R (1972) Electron microscopic studies on the trabecular meshwork in glaucoma simplex. Albrecht v Graefes Arch Klin Exp Ophthalmol 183:251-266
128. Ronnov-Jessen L, Petersen OW (1993) Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. Lab Invest 68:696-707 (Pubitemid 23202798)
129. Saika S, Ikeda K, Yamanaka O, Flanders KC, Nakajima Y, Miyamoto T, Ohnishi Y, Kao WW, Muragaki Y, Ooshima A (2005) Therapeutic effects of adenoviral gene transfer of bonemorphogenic protein-7 on a corneal alkali injury model in mice. Lab Invest 85:474-486 (Pubitemid 40523940)
130. Saika S, Ikeda K, Yamanaka O, Flanders KC, Ohnishi Y, Nakajima Y, Muragaki Y, Ooshima A (2006) Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-to-mesenchymal transition of lens epithelium in mice. Am J Physiol Cell Physiol 290:C282-C289
131. Schlötzer-Schrehardt U, Zenkel M, Küchle M, Sakai LY, Naumann GO (2001) Role of transforming growth factor-beta1 and its latent form binding protein in pseudoexfoliation syndrome. Exp Eye Res 73:765-780 (Pubitemid 34112103)
132. Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003) TGF-βsignal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol 284:F243-F252 (Pubitemid 36114687)
133. Sethi A, Jain A, Zode GS, Wordinger RJ, Clark AF (2011a) Role of TGFbeta/Smad signaling in gremlin induction of human trabecular meshwork extracellular matrix proteins. Invest Ophthalmol Vis Sci 52:5251-5259
134. Sethi A, Mao W, Wordinger RJ, Clark AF (2011b) Transforming growth factor-beta induces extracellular matrix protein cross-linking lysyl oxidase (LOX) genes in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:5240-5250
135. Shepard AR, Millar JC, Pang IH, Jacobson N, Wang WH, Clark AF (2010) Adenoviral gene transfer of active human transforming growth factor-{beta}2 elevates intraocular pressure and reduces outflow facility in rodent eyes. Invest Ophthalmol Vis Sci 51:2067-2076
136. Shuman MA, Polansky JR, Merkel C, Alvarado JA (1988) Tissue plasminogen activator in cultured human trabecular meshwork cells. Predominance of enzyme over plasminogen activator inhibitor. Invest Ophthalmol Vis Sci 29:401-405 (Pubitemid 18078035)
137. Sieber C, Kopf J, Hiepen C, Knaus P (2009) Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev 20:343-355
138. Tamm ER (2009a) The role of the ciliary body in aqueous humor dynamics: structural aspects. In: Besharse J, Dana R, Dartt D (eds) Encyclopedia of the eye. Academic Press, Oxford, pp 179-186
139. Tamm ER (2009b) The trabecular meshwork outflow pathways. Functional morphology and surgical aspects. In: Shaarawy TM, Sherwood MB, Hitchings RA, Crowston JG (eds) Glaucoma, vol II. Saunders, Elsevier, Amsterdam, pp 31-44
140. Tamm ER (2009c) The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res 88:648-655
141. Tamm ER, Fuchshofer R (2007) What increases outflow resistance in primary open-angle glaucoma? Surv Ophthalmol 52 (Suppl 2):S101-S104 (Pubitemid 350060958)
142. Tamm ER, Lütjen-Drecoll E (1996) Ciliary body. Microscop Res Tech 33:390-439 (Pubitemid 26098557)
143. Tamm E, Flügel C, Stefani FH, Rohen JW (1992) Contractile cells in the human scleral spur. Exp Eye Res 54:531-543
144. Tamm ER, Siegner A, Baur A, Lutjen-Drecoll E (1996) Transforming growth factor-beta 1 induces alpha-smooth muscle-actin expression in cultured human and monkey trabecular meshwork. Exp Eye Res 62:389-397 (Pubitemid 26150372)
145. Tamm E, Russell P, Epstein DL, Johnson DH, Piatigorsky J (1999) Modulation of Myocilin/TIGR expression in human trabecular meshwork. Invest Ophthalmol Vis Sci 40:2577-2582 (Pubitemid 29455486)
146. Tamm ER, Toris CB, Crowston JG, Sit A, Lim S, Lambrou G, Alm A (2007) Basic science of intraocular pressure. In: Weinreb RN, Brandt JD, Garway-Heath D, Medeiros F (eds) Intraocular pressure. Reports and consensus statements of the 4th global AIGS consensus meeting on intraocular pressure. Kugler, Amsterdam, pp 1-14
147. Tektas OY, Lütjen-Drecoll E (2009) Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp Eye Res 88:769-775
148. The AGIS Investigators (2000) The advanced glaucoma intervention study (AGIS). 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 130:429-440
149. Tian B, Geiger B, Epstein DL, Kaufman PL (2000) Cytoskeletal involvement in the regulation of aqueous humor outflow. Invest Ophthalmol Vis Sci 41:619-623 (Pubitemid 30158867)
150. Tian B, Gabelt BT, Geiger B, Kaufman PL (2009) The role of the actomyosin system in regulating trabecular fluid outflow. Exp Eye Res 88:713-717
151. Tomarev SI, Wistow G, Raymond V, Dubois S, Malyukova I (2003) Gene expression profile of the human trabecular meshwork: NEIBank sequence tag analysis. Invest Ophthalmol Vis Sci 44:2588-2596 (Pubitemid 36618418)
152. Tovar-Vidales T, Roque R, Clark AF, Wordinger RJ (2008) Tissue transglutaminase expression and activity in normal and glaucomatous human trabecular meshwork cells and tissues. Invest Ophthalmol Vis Sci 49:622-628
153. Tovar-Vidales T, Clark AF, Wordinger RJ (2011) Transforming growth factor-beta2 utilizes the canonical Smad-signaling pathway to regulate tissue transglutaminase expression in human trabecular meshwork cells. Exp Eye Res 93:442-451
154. Tripathi RC, Li JP, Borisuth NSC, Tripathi BJ (1993a) Trabecular cells of the eye express messenger RNA for transforming growth factor-β1 and secrete this cytokine. Invest Ophthalmol Vis Sci 34:2562-2569 (Pubitemid 23206486)
155. Tripathi RC, Borisuth NS, Kolli SP, Tripathi BJ (1993b) Trabecular cells express receptors that bind TGF-β1 and TGF-β2: a qualitative and quantitative characterization. Invest Ophthalmol Vis Sci 34:260-263 (Pubitemid 23045124)
156. Tripathi RC, Li J, Chan WFA, Tripathi BJ (1994a) Aqueous humor in glaucomatous eyes contains an increased level of TGF-β2. Exp Eye Res 58:723-727
157. Tripathi RC, Chan WFA, Li J, Tripathi BJ (1994b) Trabecular cells express the TGF-β2 gene and secrete this cytokine. Exp Eye Res 58:523-528 (Pubitemid 24249761)
158. Trivedi RH, Nutaitis M, Vroman D, Crosson CE (2011) Influence of race and age on aqueous humor levels of transforming growth factor-beta 2 in glaucomatous and nonglaucomatous eyes. J Ocul Pharmacol Ther 27:477-480
159. Varela HJ, Hernandez MR (1997) Astrocyte responses in human optic nerve head with primary open-angle glaucoma. J Glaucoma 6:303-313 (Pubitemid 28050922)
160. Wallentin N, Wickstrom K, Lundberg C (1998) Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 39:1410-1418 (Pubitemid 28307366)
161. Wang S, Hirschberg R (2003) BMP7 antagonizes TGF-beta-dependent fibrogenesis in mesangial cells. Am J Physiol Renal Physiol 284:F1006-F1013 (Pubitemid 36443585)
162. Wang S, Hirschberg R (2004) Bone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells. J Biol Chem 279:23200-23206 (Pubitemid 38685626)
163. Welge-Lüssen U, May CA, Lütjen-Drecoll E (2000) Induction of tissue transglutaminase in the trabecular meshwork by TGF-β1 and TGF-β2. Invest Ophthalmol Vis Sci 41:2229-2238
164. Wiederholt M, Thieme H, Stumpff F (2000) The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res 19:271-295 (Pubitemid 30122724)
165. Willis BC, Borok Z (2007) TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol 293:L525-L534 (Pubitemid 47358808)
166. Wordinger RJ, Agarwal R, Talati M, Fuller J, Lambert W, Clark AF (2002) 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 8:241-250 (Pubitemid 36153614)
167. Wordinger RJ, Fleenor DL, Hellberg PE, Pang IH, Tovar TO, Zode GS, Fuller JA, Clark AF (2007) Effects of TGF-beta2, BMP-4, and gremlin in the trabecular meshwork: implications for glaucoma. Invest Ophthalmol Vis Sci 48:1191-1200 (Pubitemid 351261414)
168. Wormstone IM, Tamiya S, Anderson I, Duncan G (2002) TGF-beta2-induced matrix modification and cell transdifferentiation in the human lens capsular bag. Invest Ophthalmol Vis Sci 43:2301-2308 (Pubitemid 34700662)
169. Yamamoto N, Itonaga K, Marunouchi T, Majima K (2005) Concentration of transforming growth factor beta2 in aqueous humor. Ophthalmic Res 37:29-33 (Pubitemid 40663231)
170. Yan X, Liu Z, Chen Y (2009) Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai) 41:263-272
171. Yang Z, Mu Z, Dabovic B, Jurukovski V, Yu D, Sung J, Xiong X, Munger JS (2007) Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol 176:787-793 (Pubitemid 46425539)
172. Ye H, Hernandez MR (1995) Heterogeneity of astrocytes in human optic nerve head. J Comp Neurol 362:441-452
173. Yoneda K, Nakano M, Mori K, Kinoshita S, Tashiro K (2007) Disease-related quantitation of TGF-beta3 in human aqueous humor. Growth Factors 25:160-167 (Pubitemid 350214965)
174. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R (2003) BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 9:964-968 (Pubitemid 36889942)
175. Zhao X, Russell P (2005) Versican splice variants in human trabecular meshwork and ciliary muscle. Mol Vis 11:603-608 (Pubitemid 41410215)
176. Zhao X, Ramsey KE, Stephan DA, Russell P (2004) Gene and protein expression changes in human trabecular meshwork cells treated with transforming growth factor-beta. Invest Ophthalmol Vis Sci 45:4023-4034 (Pubitemid 39411157)
177. Zhou L, Maruyama I, Li Y, Cheng EL, Yue BY (1999) Expression of integrin receptors in the human trabecular meshwork. Curr Eye Res 19:395-402
178. Zode GS, Clark AF, Wordinger RJ (2009) Bone morphogenetic protein 4 inhibits TGF-beta2 stimulation of extracellular matrix proteins in optic nerve head cells: role of gremlin in ECM modulation. Glia 57:755-766
179. Zode GS, Sethi A, Brun-Zinkernagel AM, Chang IF, Clark AF, Wordinger RJ (2011) Transforming growth factor-beta2 increases extracellular matrix proteins in optic nerve head cells via activation of the Smad signaling pathway. Mol Vis 17:1745-1758