Cytoskeletal Active Agents for Glaucoma Therapy

  • Jennifer A. Faralli
  • Marie K. Schwinn
  • Donna M. Peters
  • Paul L. Kaufman


The conventional outflow pathway, also known as the trabecular meshwork-Schlemm’s canal (TM-SC) pathway, consists of three layers. The most proximal layer to the anterior chamber consists of collagen beams wrapped with trabecular meshwork (TM) cells. The middle layer is called the juxtacanalicular region (JCT). It is composed of trabecular cells embedded in a thick matrix containing fibronectin, collagen, and laminin. This region is often regarded as the major site of aqueous humor outflow resistance due to its narrow intercellular spaces. The last layer is the inner wall of Schlemm’s canal and is made up of a monolayer of specialized endothelial cells situated on a basal lamina that is directly connected to the extracellular matrix of the JCT. The inner wall of Schlemm’s canal has a high density of pores across its surface and is thought to contribute perhaps 10% of the total resistance to aqueous humor outflow through the TM.


Actin Filament Trabecular Meshwork Myosin Light Chain Kinase Myosin Regulatory Light Chain Trabecular Meshwork Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Gong H, Tripathi RC, Tripathi BJ. Morphology of the aqueous outflow pathway. Microsc Res Tech. 1996;33:336–367.CrossRefPubMedGoogle Scholar
  2. 2.
    Llobet A, Gasull X, Gual A. Understanding trabecular meshwork physiology: a key to the control of intraocular pressure? News Physiol Sci. 2003;18:205–209.PubMedGoogle Scholar
  3. 3.
    Johnson DH, Johnson M. How does nonpenetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery [comment]. J Glaucoma. 2001;10:55–67.CrossRefPubMedGoogle Scholar
  4. 4.
    Bill A. Editorial: the drainage of aqueous humor. Invest Ophthalmol. 1975;14:1–3.PubMedGoogle Scholar
  5. 5.
    Barany EH. The mode of action of pilocarpine on outflow resistance in the eye of a primate (Cercopithecus ethiops). Invest Ophthalmol. 1962;1:712–727.PubMedGoogle Scholar
  6. 6.
    Wiederholt M, Thieme H, Stumpff F. The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res. 2000;19:271–295.CrossRefPubMedGoogle Scholar
  7. 7.
    Lepple-Wienhues A, Stahl F, Wiederholt M. Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle. Exp Eye Res. 1991;53:33–38.CrossRefPubMedGoogle Scholar
  8. 8.
    de Kater AW, Shahsafaei A, Epstein DL. Localization of smooth muscle and nonmuscle actin isoforms in the human aqueous outflow pathway. Invest Ophthalmol Vis Sci. 1992;33:424–429.PubMedGoogle Scholar
  9. 9.
    de Kater AW, Spurr-Michaud SJ, Gipson IK. Localization of smooth muscle myosin-containing cells in the aqueous outflow pathway. Invest Ophthalmol Vis Sci. 1990;31:347–353.PubMedGoogle Scholar
  10. 10.
    Rao PV, Deng P, Sasaki Y, Epstein DL. Regulation of myosin light chain phosphorylation in the trabecular meshwork: role in aqueous humor outflow facility. Exp Eye Res. 2005;80:197–206.CrossRefPubMedGoogle Scholar
  11. 11.
    Mitchell CH, Fleischhauer JC, Stamer WD, Peterson-Yantorno K, Civan MM. Human trabecular meshwork cell volume regulation. Am J Physiol Cell Physiol. 2002;283:C315-C326.PubMedGoogle Scholar
  12. 12.
    Stumpff F, Wiederholt M. Regulation of trabecular meshwork contractility. Ophthalmology. 2000;214:33–53.CrossRefGoogle Scholar
  13. 13.
    Thieme H, Stumpff F, Ottlecz A, Percicot CL, Lambrou GN, Wiederholt M. Mechanisms of action of unoprostone on trabecular meshwork contractility. Invest Ophthalmol Vis Sci. 2001;42:3193–3201.PubMedGoogle Scholar
  14. 14.
    Tian B, Geiger B, Epstein DL, Kaufman PL. Cytoskeletal involvement in the regulation of aqueous humor outflow. Invest Ophthalmol Vis Sci. 2000;41:619–623.PubMedGoogle Scholar
  15. 15.
    Tamm E, Flugel C, Stefani FH, Rohen JW. Contractile cells in the human scleral spur. Exp Eye Res. 1992;54:531–543.CrossRefPubMedGoogle Scholar
  16. 16.
    Tamm ER, Koch TA, Mayer B, Stefani FH, Lutjen-Drecoll E. Innervation of myofibroblast-like scleral spur cells in human money eyes. Invest Ophthalmol Vis Sci. 1995;36:1633–1644.PubMedGoogle Scholar
  17. 17.
    Epstein DL, Rowlette LL, Roberts BC. Acto-myosin drug effects and aqueous outflow function. Invest Ophthalmol Vis Sci. 1999;40:74–81.PubMedGoogle Scholar
  18. 18.
    Johnson DH. The effect of cytochalasin D on outflow facility and the trabecular meshwork of the human eye in perfusion organ culture. Invest Ophthalmol Vis Sci. 1997;38:2790–2799.PubMedGoogle Scholar
  19. 19.
    Kaufman PL. Pharmacologic trabeculocanalotomy. Facilitating aqueous outflow by assaulting the meshwork cytoskeleton, junctional complexes, and extracellular matrix [comment]. Arch Ophthalmol. 1992;110:34–36.PubMedGoogle Scholar
  20. 20.
    Kaufman PL, Barany EH. Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey. Invest Ophthalmol Vis Sci. 1977;16:47–53.PubMedGoogle Scholar
  21. 21.
    Kaufman PL, Bill A, Barany EH. Effect of cytochalasin B on conventional drainage of aqueous humor in the cynomolgus monkey. Exp Eye Res. 1977;25:411–414.CrossRefPubMedGoogle Scholar
  22. 22.
    Peterson JA, Tian B, Bershadsky AD, et al. Latrunculin-A increases outflow facility in the monkey. Invest Ophthalmol Vis Sci. 1999;40:931–941.PubMedGoogle Scholar
  23. 23.
    Peterson JA, Tian B, Geiger B, Kaufman PL. Effect of latrunculin-B on outflow facility in monkeys. Exp Eye Res. 2000;70:307–313.CrossRefPubMedGoogle Scholar
  24. 24.
    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;42:1029-1037 [erratum appears in Invest Ophthalmol Vis Sci 2001;42(8):1690].PubMedGoogle Scholar
  25. 25.
    Sabanay I, Gabelt BT, Tian B, Kaufman PL, Geiger B. H-7 effects on structure and fluid conductance of monkey trabecular meshwork. Arch Ophthalmol. 2000;118:955–962.PubMedGoogle Scholar
  26. 26.
    Tian B, Kaufman PL, Volberg T, Gabelt BT, Geiger B. H-7 disrupts the actin cytoskeleton and increases outflow facility. Arch Ophthalmol. 1998;116:633–643.PubMedGoogle Scholar
  27. 27.
    Ethier CR, Read AT, Chan DW. Effects of latrunculin-B on outflow facility and trabecular meshwork structure in human eyes. Invest Ophthalmol Vis Sci. 2006;47:1991–1998.CrossRefPubMedGoogle Scholar
  28. 28.
    Huber PA. Caldesmon. Int J Biochem Cell Biol. 1997;29:1047–1051.CrossRefPubMedGoogle Scholar
  29. 29.
    Chalovich JM, Sen A, Resetar A, et al. Caldesmon: binding to actin and myosin and effects on elementary steps in the ATPase cycle. Acta Physiol Scand. 1998;164:427–435.CrossRefPubMedGoogle Scholar
  30. 30.
    Marston S, Burton D, Copeland O, et al. Structural interactions between actin, tropomyosin, caldesmon and calcium binding protein and the regulation of smooth muscle thin filaments. Acta Physiol Scand. 1998;164:401–414.PubMedGoogle Scholar
  31. 31.
    Santas AJ, Bahler C, Peterson JA, et al. Effect of heparin II domain of fibronectin on aqueous outflow in cultured anterior segments of human eyes. Invest Ophthalmol Vis Sci. 2003;44:4796–4804.CrossRefPubMedGoogle Scholar
  32. 32.
    Tripathi BJ, Tripathi PC. Embryology of the Anterior Sege­ment of the Human Eye. Chapter pp 3-40. The Glaucomas, ed. R. Ritch, M. Bruce Shields, and T. Krupin. C.V. Mosby, St Lousis. 1989.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jennifer A. Faralli
    • 1
  • Marie K. Schwinn
    • 2
  • Donna M. Peters
    • 3
  • Paul L. Kaufman
    • 4
  1. 1.Department of PathologyUniversity of WisconsinMadisonUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Departments of Pathology and Laboratory Medicine and Ophthalmology and Visual SciencesUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  4. 4.Department of Ophthalmology and Visual SciencesSchool of Medicine and Public HealthMadisonUSA

Personalised recommendations