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

• Type of Material: Article
• Authors: Babak N. Safa, Emory University; Nina Sara Fraticelli Guzmán, Emory University; Guorong Li, Duke University; W. Daniel Stamer, Duke University; Andrew Feola, Emory University; Ross Ethier, Emory University
• Language: English
• Date: 2023-10-17
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2023.10.17.562754
• Title of Journal or Parent Work: bioRxiv
• Start Page: 562754
• Grant/Funding Information: Further, we note the generous financial support from The BrightFocus Foundation (postdoctoral fellowship G2021005F, BNS), NIH (K99EY035360 [BNS], T32EY007092 [NSFG], R01EY030871 [AJF], P30EY006360, P30EY005722, R01EY031710 [CRE and WDS], and R01EY030124 [WDS]), the Alfred P. Sloan Foundation G-2019-11435 (NSFG), the Georgia Research Alliance (CRE), and Department of Veterans Affairs Rehab R&D Service Career Development Awards (AJF; CDA-2; RX002342).
• Keywords: Finite Element Method; Pectinate Ligament; Glaucoma; IOP; Biomechanics
• Research Categories: Health Sciences, Opthamology; Engineering, Biomedical

Abstract

Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intraocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate ligaments (PLs) connect the iris and trabecular meshwork (TM) at the anterior chamber angle, with an unknown role in maintenance of the biomechanical stability of the aqueous outflow pathway, thus motivating this study. We conducted histomorphometric analysis and optical coherence tomography-based finite element (FE) modeling on three cohorts of C57BL/6 mice: ‘young’ (2–6 months), ‘middle-aged’ (11–16 months), and ‘elderly’ (25–32 months). We evaluated the age-specific morphology of the outflow pathway tissues. Further, because of the known pressure-dependent Schlemm’s canal (SC) narrowing, we assessed the dependence of the SC lumen area to varying IOPs in age-specific FE models over a physiological range of TM/PL stiffness values. We found age-dependent changes in morphology of outflow tissues; notably, the PLs were more developed in older mice compared to younger ones. In addition, FE modeling demonstrated that murine SC patency is highly dependent on the presence of PLs, and that increased IOP caused SC collapse only with sufficiently low TM/PL stiffness values. Moreover, the elderly model showed more susceptibility to SC collapse compared to the younger models. In conclusion, our study elucidated the previously unexplored role of PLs in the aqueous outflow pathway, indicating their function in supporting TM and SC under elevated IOP.