The Biology of Schlemm’s Canal

Abstract

All conventional outflow must cross the inner wall endothelium of Schlemm's canal (SC), which is the only continuous barrier to aqueous humor (AH) drainage from the eye. Consequently, the inner wall has developed unique features that enable both sensor and effector functions for intraocular pressure (IOP) mechanoregulation. The inner wall works as a one-way valve, allowing AH drainage in the basal-to-apical direction to facilitate outflow, while preserving the blood-aqueous barrier by preventing reflux of blood into the anterior chamber. The valve-like function of the inner wall arises from the biomechanical response of SC cells to transendothelial basal-to-apical flow, driving the formation of giant vacuoles and pores that provide pathways for AH and particulates such as pigment to cross an otherwise continuous endothelium containing tight junctions. At the same time, SC cells experience shear stress arising from circumferential flow in its lumen. Shear stress stimulates the production of signaling molecules such as nitric oxide (NO) that influence the contractility and resistance generation by the underlying trabecular meshwork (TM). Shear-mediated NO production provides a fast mechanism for outflow regulation to complement stretch-induced mechanisms that act over day-long time scales. In normotensive individuals, such mechanisms are sufficient to maintain IOP homeostasis within a narrow range throughout a lifetime. In glaucoma, however, impaired SC pore formation and increased SC/TM stiffness lead to outflow dysfunction and reduced IOP mechanosensitivity, resulting in ocular hypertension. This chapter describes the (mechano)biology of the inner wall, its importance in outflow function and IOP homeostasis, and how dysregulation contributes to ocular hypertension in glaucoma.