Fundamental Biomaterial Considerations in the Development of a 3D Model Representative of Primary Open Angle Glaucoma

Glaucoma is a leading cause of irreversible blindness globally, with primary open angle glaucoma (POAG) being the most common subset. Raised intraocular pressure is an important risk factor for POAG and is caused by a reduction in aqueous humour (AqH) outflow due to dysfunctional cellular and matrix dynamics in the eye's main drainage site, the trabecular meshwork (TM) and Schlemm's canal (SC). The TM/SC are highly specialised tissues that regulate AqH outflow; however, their exact mechanisms of AqH outflow control are still not fully understood. Emulating physiologically relevant 3D TM/S in vitro models poses challenges to accurately mimic the complex biophysical and biochemical cues that take place in healthy and glaucomatous TM/SC in vivo. With development of such models still in its infancy, there is a clear need for more well-defined approaches that will accurately contrast the two central regions that become dysfunctional in POAG; the juxtacanalicular tissue (JCT) region of the TM and inner wall endothelia of the Schlemm's canal (eSC). This review will discuss the unique biological and biomechanical characteristics that are thought to influence AqH outflow and POAG progression. Further consideration into fundamental biomaterial attributes for the formation of a biomimetic POAG/AqH outflow model will also be explored for future success in pre-clinical drug discovery and disease translation.