Investigating the Dynamic Behavior of Murine Pectinate Ligaments in Response to Intraocular Pressure Changes

Abstract

Purpose : Pectinate ligaments (PLs) are structural components of the aqueous outflow pathway in many species including mice, a common ocular hypertension model. However, the role of PLs in aqueous outflow and intraocular pressure (IOP) regulation is unclear. Recently, we investigated murine PL structure and steady-state mechanics using histomorphometry and finite element (FE) modeling [Safa+2023 and Li+2023, bioRxiv], which revealed PL structural development and increased stiffness with age, and their role in resisting Schlemm’s canal (SC) collapse by exerting tension on the trabecular meshwork (TM). However, the dynamic response of PLs to physiological changes in IOP (e.g., blinking, ocular pulse) are unknown. Here, we assessed the biomechanical response of PLs to a rapid change in IOP.

Methods : We treated murine PLs as a poroelastic (biphasic) material to evaluate their characteristic response time (τ), a measure of how long the effect of IOP perturbations persist. First, we estimated theoretically using τ~α²/H_ak [Armstrong+1984, JBME], where α=178 μm is the relevant characteristic (SC) length [Safa+2023], H_a=0.22 kPa is the PL aggregate modulus [Li+2023], and k=1 mm⁴/N.s is the hydraulic permeability [Ethier+1986, IOVS]. Second, we used an FE model, solved in FEBio, to study the irideo-corneal angle in elderly mice (25-32 months) [Safa+2023] subject to an IOP increase: 5 mmHg above baseline linearly over 0.1 sec, followed by a hold (9.9 sec).

Results : The theoretical estimation resulted in τ~2.4 min. A rapid IOP change of 5 mmHg caused a significant fluid flux through the PLs, being initiated at the anterior edge of the PLs and propagating through the PLs while decreasing in magnitude over time, dissipating >95% within 5 sec.

Conclusions : Our calculations confirmed that murine PLs have a characteristic response time (5 sec ~ 2.4 min) that is physiologically relevant for IOP fluctuations. Thus, in addition to the PLs supporting the SC against collapse, they may exert transient biomechanical effects that moderate TM and PL deformations in response to IOP fluctuations, thereby helping to stabilize aqueous outflow.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

(A) Averaged fluid velocity magnitude (mm/s) in the PL region vs. time. Note that the IOP was increased for 0.1 sec and was held constant thereafter. The flux asymptotically decreased over 5 seconds. (B) Spatial patterns of fluid velocity in PL over time. Scale bar = 50 µm