Clearing the light path: proteoglycans and their important roles in the lens and cornea

Some of the earliest studies of glycans were performed on mammalian corneas and lenses with many of the key concepts we currently recognize as being fundamental to our understanding of basic cell biology arising from these studies. Proteoglycans and their GAG side chains are essential components of the ECM of the lens capsule. They also are present in the anterior corneal epithelial basement membrane and the posterior (Decemet's) basement membrane, and they organize collagen fiber diameters and spacing in the corneal stroma to maintain stromal clarity. Studies using genetically engineered mice and characterization of spontaneously arising mutations in genes controlling proteoglycan synthesis have generated new insight into the roles played by proteoglycans in signal transduction. We now know that proteoglycans and GAGs can regulate cell signaling and the maintenance of avascularity and immune privilege that are hallmarks of these tissues. In addition, proteoglycan-rich matrices provide the pathways for immune cells to populate the surface of the lens as a response to corneal wounding and in a model of Experimental Autoimmune Uveitis. Here we describe what is known about proteoglycans and GAGs in the cornea and lens. This knowledge has begun to provide promising leads into new proteoglycan-based treatments aimed at restoring and maintaining homeostasis in the cornea. Future studies are needed to determine how these new drugs impact the recruitment of immune cells to the lens for functions in restoring/maintaining homeostasis in the eye.