Chapter Eighteen - Intraocular Pressure and the Mechanisms Involved in Resistance of the Aqueous Humor Flow in the Trabecular Meshwork Outflow Pathways

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Abstract

Intraocular pressure (IOP), the critical risk factor for glaucoma, is generated and maintained by the aqueous humor circulation system. Aqueous humor is secreted from the epithelial layers of the ciliary body and exits the eye through the trabecular meshwork or the uveoscleral outflow pathways. IOP builds up in response to a resistance to aqueous humor flow in the trabecular outflow pathways. The trabecular outflow resistance is localized in the inner wall region, which comprises the juxtacanalicular connective tissue (JCT) and the inner wall endothelium of Schlemm's canal (SC). Outflow resistance in this region is lowered through the relaxation of contractile myofibroblast-like cells in trabecular meshwork and the adjacent scleral spur, or the contraction of the ciliary muscle. In primary open-angle glaucoma, the most frequent form of glaucoma, outflow resistance of the inner wall region is typically higher than normal. There is evidence that the increase in resistance is related to characteristic biological changes in the resident cells of the JCT, which more and more acquire the structural and functional characteristics of contractile myofibroblasts. The changes involve an augmentation of their actin cytoskeleton and of their surrounding fibrillary extracellular matrix, which connects to JCT cells via integrins. This scenario leads to an overall stiffening of the inner wall region, and is modulated by transforming growth factor-β/connective tissue growth factor signaling. Essentially comparable changes appear to occur in SC endothelial cells. Stiffening of JCT and SC cells is very likely a critical causative factor for the increase in trabecular outflow resistance in POAG.

Section snippets

Intraocular Pressure and Aqueous Humor Outflow

Glaucoma, the leading cause of irreversible blindness throughout the world,1 is a chronic, progressive optic nerve neuropathy, in which optic nerve axons are damaged at the optic disc, the site of their exit from the eye. In several prospective randomized multi-center studies, intraocular pressure (IOP) has been identified as the critical causative risk factor for glaucoma and, consequently, the reduction of IOP delays or prevents the damage of optic nerve axons.2, 3, 4, 5, 6, 7, 8 This chapter

Trabecular Meshwork

The trabecular meshwork comprises connective tissue lamellae that are covered by flat, epithelial-like trabecular meshwork cells, which rest on a basal lamina and are of neural crest origin.11, 17 Anteriorly, the trabecular lamellae attach to the peripheral cornea in a region termed Schwalbe's line. Posteriorly, the trabecular lamellae are connected to the stroma of the ciliary body and iris at their junction, and to the scleral spur (Fig. 1). There is considerable evidence that the region

Schlemm's Canal

Schlemm's canal is a modified capillary blood vessel that transiently forms intra- and intercellular pores (Fig. 2), which can acquire unusually large diameters of up to 1 μm.16 As result, the hydraulic conductivity of Schlemm's canal is the highest in the body and even higher than that in the fenestrated capillaries of the glomeruli in the kidney or the sinusoids in the liver.16 Aqueous humor passes Schlemm's canal endothelial cells in a basal-luminal direction, which results in the formation

Outflow Resistance

It is generally accepted that the outflow resistance of the trabecular outflow pathways is localized in the inner wall region comprising the juxtacanalicular tissue and the inner wall endothelium of Schlemm's canal.16 There are three potential mechanisms, which may be involved in the generation of trabecular outflow resistance and which will be discussed here. (1) Outflow resistance largely depends on the quality and quantity of the extracellular matrix in the extracellular spaces of the

Contractile Mechanisms in the Trabecular Outflow Pathways

There are two contractile systems that influence the architecture of the trabecular outflow pathways to modify outflow resistance in the inner wall region. The ciliary muscle is attached to the scleral spur, the posterior attachment of the trabecular meshwork, via tendon-like structures.34, 35 Consequently, contraction of the ciliary muscle results in a changed geometry of the trabecular outflow pathways and reduces outflow resistance in the inner wall region. Experimental disinsertion of

Resistance of the Trabecular Outflow Pathways in Primary Open-Angle Glaucoma

The juxtacanalicular tissue of patients with POAG develops very characteristic structural changes in the course of the disease.44 The quality and quantity of the elastic fibers sheath material in the cribriform plexus changes, and there is an increase of material originally described as “sheath-derived plaques.”45, 46 The increase in the amounts of sheath-derived plaque material in the juxtacanalicular tissue correlates with the severity of optic nerve damage in POAG.47 However, the amount of

References (55)

  • B. Hinz et al.

    The myofibroblast: one function, multiple origins

    Am J Pathol

    (2007)
  • C. Flügel et al.

    Different cell populations in bovine trabecular meshwork: an ultrastructural and immunohistochemical study

    Exp Eye Res

    (1991)
  • M. Wiederholt et al.

    The regulation of trabecular meshwork and ciliary muscle contractility

    Prog Retin Eye Res

    (2000)
  • B. Tian et al.

    The role of the actomyosin system in regulating trabecular fluid outflow

    Exp Eye Res

    (2009)
  • O.Y. Tektas et al.

    Structural changes of the trabecular meshwork in different kinds of glaucoma

    Exp Eye Res

    (2009)
  • R. Fuchshofer et al.

    Modulation of extracellular matrix turnover in the trabecular meshwork

    Exp Eye Res

    (2009)
  • B. Junglas et al.

    Connective tissue growth factor induces extracellular matrix deposition in human trabecular meshwork cells

    Exp Eye Res

    (2009)
  • B. Junglas et al.

    Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork

    Am J Pathol

    (2012)
  • P.P. Pattabiraman et al.

    RhoA GTPase-induced ocular hypertension in a rodent model is associated with increased fibrogenic activity in the trabecular meshwork

    Am J Pathol

    (2015)
  • S. Resnikoff et al.

    Global data on visual impairment in the year 2002

    Bull World Health Organ

    (2004)
  • M.C. Leske et al.

    Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial

    Arch Ophthalmol

    (2003)
  • D.R. Anderson

    Collaborative normal tension glaucoma study

    Curr Opin Ophthalmol

    (2003)
  • M.A. Kass et al.

    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

    (2002)
  • M.O. Gordon et al.

    The ocular hypertension treatment study: baseline factors that predict the onset of primary open-angle glaucoma

    Arch Ophthalmol

    (2002)
  • The AGIS Investigators

    The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration

    Am J Ophthalmol

    (2000)
  • Collaborative Normal-Tension Glaucoma Study Group

    Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures

    Am J Ophthalmol

    (1998)
  • Collaborative Normal-Tension Glaucoma Study Group

    The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative normal-tension glaucoma study group

    Am J Ophthalmol

    (1998)
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