Schlemm??s Canal Endothelia, Lymphatic, or Blood Vasculature?

Abstract

In the human eye, the final barrier for aqueous humor to cross before returning to systemic circulation is the inner wall of Schlemm's canal. Unfortunately, the specific contribution of the inner wall to total outflow resistance in the conventional pathway is unknown in both normal and glaucomatous eyes. To better understand inner wall physiology, we contrasted it with 2 specialized continuous endothelia, initial lymphatic, and blood capillary endothelia. Specifically, we compare their developmental origin, morphology, junctional complexes, microenvironment, and physiologic responses to different biomechanical factors. Our evaluation concludes that the inner wall of Schlemm's canal is unique, sharing extraordinary characteristics with both types of specialized endothelia in addition to having distinctive features of its own.

The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel

“…It is the final barrier for the AH before returning to systemic circulation, but its specific contribution to AH outflow resistance is unknown (4). Interestingly, glaucoma patients have a smaller SC (9), and agenesis or hypoplasia of the SC has been implicated in primary congenital glaucomas (10)(11)(12)(13).…”

“…Interestingly, glaucoma patients have a smaller SC (9), and agenesis or hypoplasia of the SC has been implicated in primary congenital glaucomas (10)(11)(12)(13). However, it is still unknown whether the SC is a component of the blood or the lymphatic vascular system (1,4,14).…”

“…Furthermore, the SC has a continuous endothelial cell (EC) monolayer that lacks fenestrations, lies on a discontinuous basement membrane, is not enclosed by pericytes or smooth muscle cells, and is subjected to a basal-to-apical direction of flow, like lymphatic capillaries (1,4,17,18). Moreover, connecting fibrils extending from SC ECs into the surrounding cribriform plexus may be involved in preventing SC collapse (17), analogously to the anchoring filaments found in lymphatic vessels (4,19,20).…”

“…AH is prod¡¡uced by the ciliary epithelium, sieved through the trabecular meshwork (TM), taken up by the Schlemm's canal (SC), and drained into episcleral (ES) veins via aqueous veins (AVs) (1,4). The trabecular outflow pathway accounts for 70%-90% of AH removal in humans.…”

Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity

“…Schlemm's canal (SC) is an endothelium-lined vascular channel that encircles the margin of the cornea and drains aqueous humor, which is produced in the ciliary body and supplies the cornea and lens with nutrients through collector channels into the circulation (1,2). SC is a conventional aqueous humor outflow (AHO) pathway accounting for the majority of AHO and is responsible for appropriate resistance against it to maintain a balance between the secretion and drainage of aqueous humor, thereby controlling intraocular pressure (IOP) (3,4).…”