title: Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction.
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.
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA. Electronic address: dan.stamer@duke.edu.
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Stamer
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Sietse T
authors.initials: ST
authors.lastname: Braakman
authors.affiliation: Department of Ophthalmology, Novartis Institutes of BioMedical Research, Cambridge, MA 02139, USA.
authors.forename: Enhua H
authors.initials: EH
authors.lastname: Zhou
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA; Department of Ophthalmology, Emory University, Atlanta, GA 30322, USA.
authors.forename: C Ross
authors.initials: CR
authors.lastname: Ethier
authors.affiliation: Program in Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115, USA; Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Overby
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL, US; Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA; Department of Ophthalmology Engineering, Northwestern University, Chicago, IL, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
mesh_terms: D001082:Aqueous Humor / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D005901:Glaucoma / Q000503:physiopathology*; D006801:Humans; D042541:Intracellular Space / Q000502:physiology; D007429:Intraocular Pressure / Q000502:physiology*; D010477:Perfusion; D014129:Trabecular Meshwork / Q000502:physiology*
keywords: Aqueous humor; Conventional outflow; Glaucoma; Ocular hypertension; Schlemm's canal; Trabecular meshwork