Glaucoma-associated myocilin: A better understanding but much more to learn

Over a decade has passed since myocilin was identified as the first gene linked to early and late-onset primary open-angle glaucoma. During this time, considerable effort has been put forth to understand the functional role myocilin has in normal and glaucomatous eyes. Myocilin is expressed in many ocular and non-ocular tissues, is found in both intracellular and extracellular spaces, and has been linked to elevations in intraocular pressure. Mutations in the myocilin gene that have been associated with glaucoma appear to confer a gain-of-functional activity rather than loss of function. Unfortunately, what the normal function of myocilin is and how alterations in the function can confer a glaucoma phenotype have yet to be elucidated. We will review the current understanding of myocilin with special emphasis on the structural makeup of the myocilin gene and protein, its possible physiological roles internal and external to ocular cells, the regulation of intraocular pressure as evidenced through the use of perfusion culture systems and animal models, and as a causative agent in some forms of glaucoma.