Unconventional aqueous humor outflow: A review

Abstract

Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.

Impaired angiopoietin/Tie2 signaling compromises Schlemm’s canal integrity and induces glaucoma

“…Our findings highlight SC as a functional reservoir of AHO as well as a main structure for glaucomagenesis when severely impaired. Although it has been long debated (43)(44)(45), recent studies indicate that AHOc, rather than AHOu, is a primary route for AHO in C57BL/6J mice (46,47), similar to that in humans. We note that a more than 50% reduction in SC area and a marked reduction in transcytotic activity in SC ECs are prerequisites for the significant elevation of IOP, retinal neuronal damage, and impairment of retinal ganglion cell function.…”

Comparison of Aqueous Outflow Facility Measurement by Pneumatonography and Digital Schiøtz Tonography

“…It returns to the venous system primarily through the trabecular or conventional pathway, but also exits by the uveoscleral or unconventional route. 1,2 The ease of aqueous humor outflow through the conventional path is usually expressed as outflow facility in microliters per minute per millimeter of Hg pressure difference (μL/min/mm Hg). 3 Impairment of aqueous humor outflow, which decreases outflow facility, elevates IOP and is a central tenet of pathophysiology and treatment of ocular hypertension and glaucoma.…”

Active Lymphatic Drainage From the Eye Measured by Noninvasive Photoacoustic Imaging of Near-Infrared Nanoparticles

“…3,4 Two aqueous outflow pathways have been identified as contributing to aqueous drainage and include the conventional pathway through trabecular meshwork into the venous system, and the unconventional pathway passing through the iris, ciliary body, choroid, and the sclera, also called uveoscleral pathway. 5,6 An alternate route, called the uveolymphatic pathway has been proposed based on the finding of ciliary body lymphatics and the detection of intracamerally injected tracer in ciliary body lymphatic channels and cervical lymph nodes. 7,8 As lymphatics in ciliary body were not detected by others, 9,10 their existence remains controversial.…”