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.

Keywords: Biological transport phenomena; Blood-aqueous barrier; Diffusion; Glaucoma; Schlemm's canal endothelium.

Figure 1

A schematic representation of a pore through the inner wall endothelium of Schlemm’s canal. Aqueous humor passes through the pore in the basal-to-apical direction, which contributes to anterograde mass transport due to advection. Retrograde mass transport occurs via diffusion in the opposite (apical-to-basal) direction. The luminal aspect of the pore coincides with x = 0 and the luminal concentration is assumed to be c_SC. The cell thickness at the pore is L and the diameter of the pore is D_tot.

Figure 2

The predicted relationship between the solute concentration ratio across a pore $\left(\frac{c_{JCT}}{c_{SC}}\right)$ versus the molecular weight of the diffusing solute, as determined by combining Equations 3–6 (black curve). Red points show the $\frac{c_{JCT}}{c_{SC}}$ ratio using the experimentally-determined values for the diffusion coefficient for glucose, thrombin (bovine), albumin, prothrombin (bovine) and γG-immunoglobulin (IgG), values of which were obtained from Harmison et al., 1961, Lamy and Waugh, 1953, Levick and Smaje, 1987 and Tyn and Gusek, 1990. Deviations from the curve are due to differences between the estimate provided by Equation 5 and the true diffusion coefficient. For solutes smaller than 10 kDa, the $\frac{c_{JCT}}{c_{SC}}$ ratio is 10% or more, while for larger proteins, such as albumin, prothrombin and IgG, the $\frac{c_{JCT}}{c_{SC}}$ ratio is 1% or less. This suggests that SC endothelium forms an effective barrier against retrograde transport of large molecular weight solutes and serum proteins into the JCT, consistent with its role as part of the BAB.