The Juxtacanalicular Region of Ocular Trabecular Meshwork: A Tissue with a Unique Extracellular Matrix and Specialized Function

The trabecular meshwork (TM) is a filter-like tissue located in the anterior segment of the eye. It is composed of a series of fenestrated beams through which aqueous humor flows to exit the anterior chamber via Schlemm's canal. The primary function of the TM is to regulate the flow of aqueous humor in order to establish intraocular pressure (IOP). Dysregulated aqueous humor outflow causes elevated IOP, which is a primary risk factor for glaucoma. The region of the TM implicated in establishing IOP lies adjacent to Schlemm's canal and is called the juxtacanalicular tissue (JCT) or cribriform region. Recent advanced light microscopy studies suggest that the JCT can be subdivided into inner and outer zones based on the localization of certain extracellular matrix (ECM) molecules. By comparing the ECM of the JCT to other connectives tissues and disease processes, this review outlines the evidence for two new concepts in TM biology: (1) continuous maintenance ECM remodeling, which may be critical in order to preserve open aqueous humor flow channels by releasing trapped debris and associated ECM fragments from the outflow pathways; (2) the JCT ECM as a barrier to functionally isolate the aqueous outflow channels. The ECM surrounding the outflow channels in the JCT may function to sequester small active regulatory molecules and prevent them from aberrantly modulating outflow resistance. These adaptations point to a distinctive tissue that has evolved transient ECM remodeling processes in order to regulate aqueous humor outflow and maintain rigorous control of IOP.