title: Transport across Schlemm's canal endothelium and the blood-aqueous barrier.
abstract: The majority of trabecular outflow likely crosses Schlemm's canal (SC) endothelium through micron-sized pores, and SC endothelium provides the only continuous cell layer between the anterior chamber and episcleral venous blood. SC endothelium must therefore be sufficiently porous to facilitate outflow, while also being sufficiently restrictive to preserve the blood-aqueous barrier and prevent blood and serum proteins from entering the eye. To understand how SC endothelium satisfies these apparently incompatible functions, we examined how the diameter and density of SC pores affects retrograde diffusion of serum proteins across SC endothelium, i.e. from SC lumen into the juxtacanalicular tissue (JCT). Opposing retrograde diffusion is anterograde bulk flow velocity of aqueous humor passing through pores, estimated to be approximately 5 mm/s. As a result of this relatively large through-pore velocity, a mass transport model predicts that upstream (JCT) concentrations of larger solutes such as albumin are less than 1% of the concentration in SC lumen. However, smaller solutes such as glucose are predicted to have nearly the same concentration in the JCT and SC. In the hypothetical case that, rather than micron-sized pores, SC formed 65 nm fenestrae, as commonly observed in other filtration-active endothelia, the predicted concentration of albumin in the JCT would increase to approximately 50% of that in SC. These results suggest that the size and density of SC pores may have developed to allow SC endothelium to maintain the blood-aqueous barrier while simultaneously facilitating aqueous humor outflow.
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom.
authors.forename: Sietse T
authors.initials: ST
authors.lastname: Braakman
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Moore
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom; Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA.
authors.forename: C Ross
authors.initials: CR
authors.lastname: Ethier
authors.affiliation: Department of Bioengineering, Imperial College London, London, United Kingdom. Electronic address: d.overby@imperial.ac.uk.
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Overby
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D018916:Blood-Aqueous Barrier / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism* / Q000648:ultrastructure; D005901:Glaucoma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D012590:Sclera / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism
keywords: Biological transport phenomena; Blood-aqueous barrier; Diffusion; Glaucoma; Schlemm's canal endothelium