Aging and intraocular pressure homeostasis in mice

Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma. Age and elevated intraocular pressure (IOP) are the two primary risk factors for the second leading cause of blindness in the world, glaucoma. Despite a number of age-related changes to the IOP-regulating tissues of the eye that should impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), we observed that IOP was stable with age. Thus, healthy eyes appear to have significant functional reserve for IOP regulation, but when combined with other underlying factors, such as genetic susceptibility, are predicted to increase risk for elevated IOP and glaucoma.image