Glaucoma – ‘A Stiff Eye in a Stiff Body’

Glaucoma is a progressive, age-related optic neuropathy, whereby the prevalence increases sharply over the age of 60 and is associated with increased systemic tissue stiffness. On a molecular basis, this is associated with increased deposition of collagen and loss of elastin structure, resulting in aberrant biomechanical compliance and reduced tissue elasticity. Increased tissue stiffness is a known driver of myofibroblast activation and persistence, especially in chronic cellular injuries via mechanotransduction pathways mediated by integrins and focal adhesion kinases. Evidence from histological and imaging studies plus force measurements of glaucomatous eyes show that several ocular tissues are stiffer than normal, healthy age-matched controls including the trabecular meshwork, Schlemm's canal, cornea, sclera and the lamina cribrosa. This is associated with increased extracellular matrix deposition and fibrosis. This review reports on the evidence to support the concept that glaucoma represents 'a stiff eye in a stiff body' and addresses potential mechanisms to attenuate this.