Aqueous outflow: Segmental and distal flow

Abstract

A prominent risk factor of primary open-angle glaucoma is ocular hypertension, a pathologic state caused by impaired outflow of aqueous humor through the trabecular meshwork within the iridocorneal angle. The juxtacanalicular region of the trabecular meshwork and the inner wall of Schlemm canal have been identified as the main contributors to aqueous outflow resistance, and both extracellular matrix within the trabecular meshwork and trabecular meshwork cell shape have been shown to affect outflow. Overexpression of multiple ECM proteins in perfused cadaveric human eyes has led to increased outflow resistance and elevated IOP. Pharmacologic agents targeting trabecular meshwork cytoskeletal arrangements have been developed after multiple studies demonstrated the importance of cell shape on outflow. Several groups have shown that aqueous outflow occurs only at certain segments of the trabecular meshwork circumferentially, a concept known as segmental flow. This is based on the theory that aqueous outflow is dependent on the presence of discrete pores within the Schlemm canal. Segmental flow has been described in the eyes of multiple species, including primate, bovine, mouse, and human samples. While the trabecular meshwork appears to be the major source of resistance, trabecular meshwork bypass procedures have been unable to achieve the degree of IOP reduction observed with trabeculectomy, reflecting the potential impact of distal flow, or flow through Schlemm canal and collector channels, on outflow. Multiple studies have demonstrated that outflow occurs preferentially near collector channels, suggesting that these distal structures may be more important to aqueous outflow than previously believed.

Diurnal Variations in the Morphology of Schlemm's Canal and Intraocular Pressure in Healthy Chinese: An SS-OCT Study

“…The outflow of aqueous humor has its segmental patterns around the SC circumference, and the majority of AH outflow is likely through the inferior collector channels. 25,26 Overall, the distal flow structures (e.g., collector channels and episcleral veins) may be have more importance than previously believed. Our results showed that the SC parameters of inferior quadrant were smaller than the other three quadrants.…”

Aqueous Angiography with Fluorescein and Indocyanine Green in Bovine Eyes

“…Results demonstrate IOP lowering but inconsistent success. 1,2 One hypothesis to explain this variability is that consistent placement of these surgeries (always in the nasal quadrant of the eye) in the setting of inconsistent aqueous humor outflow (AHO) anatomy 3 may be the problem. Multiple methods have demonstrated segmental AHO as opposed to 360° uniform and circumferential AHO patterns.…”

“…After the introduction of any tracer into the AC, the tracer ultimately accumulates on the ocular surface at severed episcleral veins. 3,20 This normally would not happen in test subjects with intact eyes as tracer leaving the AC eventually moves out of the eye through the episcleral veins and towards the systemic venous circulation. Given this limitation, one cannot perform aqueous angiography, document an angiographic pattern, conduct a manipulation (pharmacologic or surgical), and repeat aqueous angiography to query the effects.…”

Secreted Protein Acidic and Rich in Cysteine in Ocular Tissue

“…Given SPARC's effect on collagen fibril diameter, variation in the spatial expression of SPARC throughout the TM may be a mechanism for the generation of segmental flow that occurs in the human and murine eye. 84 SPARC overexpression in human TM cells, conversely, resulted in elevated IOP in an ex vivo anterior chamber perfusion chamber model. 85 Overexpression of SPARC within TM cell cultures and within the JCT of perfused anterior segments resulted in elevated protein levels of fibronectin and collagens I and IV.…”