Finite element analysis of the pressure-induced deformation of Schlemm’s canal endothelial cells

Abstract

The endothelial cells lining the inner wall of Schlemm’s canal (SC) in the eye are relatively unique in that they support a basal-to-apical pressure gradient that causes these cells to deform, creating giant vacuoles and transendothelial pores through which the aqueous humor flows. Glaucoma is associated with an increased resistance to this flow. We used finite element modeling and estimates of cell modulus made using atomic force microscopy to characterize the pressure-induced deformation of SC cells and to estimate the maximum pressure drop that SC cells can support. We examined the effects of cell geometry, cell stiffness, and the contribution of the cell cortex to support the pressure-generated load. We found that the maximum strain generated by this loading occurs at the points of cell–substrate attachment and that the cortex of the cells bears nearly all of this load. The ability of these cells to support a significant transcellular pressure drop is extremely limited (on the order of 5 mmHg or less) unless these cells either stiffen very considerably with increasing deformation or have substantial attachments to their substratum away from their periphery. This puts limits on the flow resistance that this layer can generate, which has implications regarding the site where the bulk of the flow resistance is generated in healthy and glaucomatous eyes.

Increased stiffness and flow resistance of the inner wall of Schlemm’s canal in glaucomatous human eyes

“…5B and 1-μm tip results in Table 1). This may be caused by extracellular matrix immediately underlying the Schlemm's canal cells [typical in vivo Schlemm's canal cell thickness is 0.2 to 1.5 μm (27,28)]. One attractive candidate for this greatly stiffened layer is the basal lamina (and/or fibrillar extracellular matrix components attached to it) underlying the inner-wall endothelium of Schlemm's canal.…”

Transport across Schlemm's canal endothelium and the blood-aqueous barrier

“…The numerical value of V SC (3.9 ± 1.1 µm/s; Table 1) is noteworthy because it is approximately 3-fold larger than the superficial filtration velocity across the renal glomerulus (1.2 µm/s † ), suggesting that the inner wall accommodates possibly the largest transendothelial filtration velocity of any endothelium in the body. Furthermore, for an average SC endothelial cell thickness of 0.5 µm (Vargas-Pinto et al, 2014), the value of V SC indicates that on average each SC cell facilitates flow at a rate nearly eight times its own volume each second. These observations strongly argue for a highly conductive pathway for flow across the inner wall, namely through pores (Johnson, 2006), and imply that active AH transport (e.g., via ‘macro pinocytosis’ (Tripathi, 1972)) cannot be the primary mechanism of AH flow across the inner wall.…”

One-year interim comparison of canaloplasty in primary open-angle glaucoma following failed filtering surgery with primary canaloplasty

“…These configuration changes may rebuild the pressure gradient from AC to episcleral vein, which push aqueous outflow 16. Meanwhile, persistent mechanical strength might induce some changes in cytoskeleton of TM and SCE that may further lead to extracellular matrix and cellularity changes 17 18…”