Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction

W. Daniel Stamer*, Sietse T. Braakman, Enhua H. Zhou, C. Ross Ethier, Jeffrey J. Fredberg, Darryl R. Overby, Mark Johnson

*Corresponding author for this work

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, interact in the juxtacanalicular tissue (JCT) region of the conventional outflow tract to regulate outflow resistance. Unlike endothelial cells lining the systemic vasculature, endothelial cells lining the inner wall of SC support a transcellular pressure gradient in the basal to apical direction, thus acting to push the cells off their basal lamina. The resulting biomechanical strain in SC cells is quite large and is likely to be an important determinant of endothelial barrier function, outflow resistance and intraocular pressure. This review summarizes recent work demonstrating how biomechanical properties of SC cells impact glaucoma. SC cells are highly contractile, and such contraction greatly increases cell stiffness. Elevated cell stiffness in glaucoma may reduce the strain experienced by SC cells, decrease the propensity of SC cells to form pores, and thus impair the egress of aqueous humor from the eye. Furthermore, SC cells are sensitive to the stiffness of their local mechanical microenvironment, altering their own cell stiffness and modulating gene expression in response. Significantly, glaucomatous SC cells appear to be hyper-responsive to substrate stiffness. Thus, evidence suggests that targeting the material properties of SC cells will have therapeutic benefits for lowering intraocular pressure in glaucoma.

Original languageEnglish (US)
Pages (from-to)86-98
Number of pages13
JournalProgress in Retinal and Eye Research
Volume44
DOIs
StatePublished - Jan 1 2015

Fingerprint

Intraocular Pressure
Biomechanical Phenomena
Endothelium
Glaucoma
Aqueous Humor
Endothelial Cells
Trabecular Meshwork
Ocular Hypertension
Basement Membrane
Gene Expression
Pressure

Keywords

  • Aqueous humor
  • Conventional outflow
  • Glaucoma
  • Ocular hypertension
  • Schlemm's canal
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Stamer, W. Daniel ; Braakman, Sietse T. ; Zhou, Enhua H. ; Ethier, C. Ross ; Fredberg, Jeffrey J. ; Overby, Darryl R. ; Johnson, Mark. / Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction. In: Progress in Retinal and Eye Research. 2015 ; Vol. 44. pp. 86-98.
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Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction. / Stamer, W. Daniel; Braakman, Sietse T.; Zhou, Enhua H.; Ethier, C. Ross; Fredberg, Jeffrey J.; Overby, Darryl R.; Johnson, Mark.

In: Progress in Retinal and Eye Research, Vol. 44, 01.01.2015, p. 86-98.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction

AU - Stamer, W. Daniel

AU - Braakman, Sietse T.

AU - Zhou, Enhua H.

AU - Ethier, C. Ross

AU - Fredberg, Jeffrey J.

AU - Overby, Darryl R.

AU - Johnson, Mark

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AB - Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, interact in the juxtacanalicular tissue (JCT) region of the conventional outflow tract to regulate outflow resistance. Unlike endothelial cells lining the systemic vasculature, endothelial cells lining the inner wall of SC support a transcellular pressure gradient in the basal to apical direction, thus acting to push the cells off their basal lamina. The resulting biomechanical strain in SC cells is quite large and is likely to be an important determinant of endothelial barrier function, outflow resistance and intraocular pressure. This review summarizes recent work demonstrating how biomechanical properties of SC cells impact glaucoma. SC cells are highly contractile, and such contraction greatly increases cell stiffness. Elevated cell stiffness in glaucoma may reduce the strain experienced by SC cells, decrease the propensity of SC cells to form pores, and thus impair the egress of aqueous humor from the eye. Furthermore, SC cells are sensitive to the stiffness of their local mechanical microenvironment, altering their own cell stiffness and modulating gene expression in response. Significantly, glaucomatous SC cells appear to be hyper-responsive to substrate stiffness. Thus, evidence suggests that targeting the material properties of SC cells will have therapeutic benefits for lowering intraocular pressure in glaucoma.

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