Aging and intraocular pressure homeostasis in mice

Abstract

Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the most common 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 concluded 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.

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway

“…One factor suggested to influence PL structure is age [20]. While the effect of aging on PLs was not a primary focus of this work (see [23]), our models were based on images from different aged animals.…”

“…For further details of these experimental procedures, please see Li et al . (Li et al, 2023, 2021, 2019).…”

“…In the second type of OCT image (Iris-OCT, Group 3), the OCT scan head was placed near the corneal apex to acquire images of half of the anterior chamber at IOPs of 10, 15, and 20 mmHg. Additional IOP steps were also used but were not needed in this study (Lee et al, 2021; Li et al, 2023).…”

“…Please note that the age grouping used in this study essentially corresponded to those reported in our related paper (Li et al, 2023).…”

“…0.26 μm/pixel) to visualize the outflow pathway tissues (Figure 1). For further details of these experimental procedures, please see Li et al [23][24][25].…”