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

Abstract

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. KeywordsExtracellular matrix; Trabecular meshwork; Glaucoma; Outflow resistance; Intraocular pressure The Juxtacanalicular Trabecular MeshworkThe TM is a triangular-shaped tissue that is located in the scleral sulcus of the anterior chamber of the eye. The TM can be divided into separate regions based on anatomical location, which differ in both structure and function: the uveal and corneoscleral meshworks, the insert region, and the juxtacanalicular region (JCT) (Figure 1). The corneoscleral and uveal meshworks are comprised of fenestrated beams of lamellae, with large intertrabecular spaces between adjacent sheets [1]. These intertrabecular spaces decrease in size and the lamellae become slightly flatter as the corneoscleral meshwork transitions into the JCT region. The JCT is the deepest area of the tissue that lies adjacent to the inner wall (IW) endothelium of Schlemm's canal [2]. This area of tissue is approximately 2-20 μm thick. Unlike the uveal and corneoscleral meshworks, the JCT is not arranged into lamellae structures, but rather it is composed of a loosely arranged extracellular matrix (ECM) in which a sparse number of JCT cells are embedded [2]. These cells are separated from the IW endothelium, although they can extend processes that communicate with both IW cells and TM cells resident in the corneoscleral meshwork [3,4]. The ECM is highly hydrated and provides a conduit for aqueous humor to traverse the JCT and exit the anterior cham...

Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells

“…Elevated IOP results from increased resistance to aqueous humor outflow in the juxtacanalicular region of the conventional outflow pathway where the trabecular meshwork (TM) and Schlemm’s canal inner wall cells interact ( Brubaker, 1991 ). Human trabecular meshwork (HTM) cells within the juxtacanalicular tissue are surrounded by a complex extracellular matrix (ECM), which is primarily composed of non-fibrillar and fibrillar collagens, elastic fibrils, proteoglycans and the glycosaminoglycan hyaluronic acid ( Acott and Kelley, 2008 ; Tamm, 2009 ; Hann and Fautsch, 2011 ; Keller and Acott, 2013 ; Abu-Hassan et al, 2014 ). In addition to providing structural support, the ECM imparts biochemical signals (e.g., hormones, growth factors and diffusible morphogens) and mechanical cues (e.g., matrix stiffness; tensile, compressive and shear forces; topographical strain) to regulate cell behaviors ( Frantz et al, 2010 ).…”

Effects of Netarsudil-Family Rho Kinase Inhibitors on Human Trabecular Meshwork Cell Contractility and Actin Remodeling Using a Bioengineered ECM Hydrogel

“…In the juxtacanalicular tissue region, TM cells reside embedded within a soft 3D ECM comprised of fibrillar and non-fibrillar collagens, elastic fibrils, glycosaminoglycans, proteoglycans, and matricellular proteins (25)(26)(27)(28)(29). This is in stark contrast to conventional 2D tissue culture substrates that are known to create non-physiological culture conditions (30,31).…”

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

“…To depict viscobeads occlusion in the AH outflow pathway, we developed a simplified model featuring three layers-UM, CM and JCT-each characterized by pore sizes falling within a 1-20 μm range [37][38][39] (Fig. 1E-DF).…”