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

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness in humans. Blindness in glaucoma is associated with intraocular pressure (IOP), which is generated and regulated by the tissues of the aqueous outflow pathway. One of the main components of the aqueous humor pathway are the pectinate ligaments (PLs) that connect iris and trabecular meshwork at the anterior chamber angle. However, their role in helping maintain the biomechanical stability of murine aqueous outflow pathway is unknown, thus motivating this study. In this work, we conducted histomorphometric analysis and optical coherence tomographic-imaging-based finite element (FE) modeling on three age cohorts of C57BL/6 mice: 'young' (2-6 months), 'middle-aged' (11-16 months), and 'elderly' (29-32 months). We also evaluated the age-specific morphometric characteristics of the outflow pathway tissues, specifically the trabecular meshwork (TM) and Schlemm's canal (SC). Further, because of the known pressure-dependent narrowing of the SC lumen in humans and mice, we assessed the sensitivity of the SC lumen area (SCLA) to varying IOPs in age-specific FE models in a physiological range of TM and PL stiffness values. We found age-dependent changes in morphological characteristics of outflow tissues; notably, the PLs were more developed in older compared to younger mice. In addition, our FE analysis demonstrated that the patency of SC in the mouse is highly dependent on the presence of PLs, and that increased IOP caused SC collapse only when TM/PL stiffness was sufficiently low. In particular, young and middle-aged mice showed a lower susceptibility to SC collapse under elevated IOP compared to elderly mice. In conclusion, our study has elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in biomechanically supporting TM and SC under elevated IOP.