Biomechanics of the trabecular meshwork: how far have we come?
Purpose: The etiology of glaucoma is unknown, although the disease is known to be associated with elevated intraocular pressure and a stiffening of the trabecular meshwork (TM) and Schlemm’s canal (SC) endothelium. The juxtacanalicular connective tissue of the TM and the basement membrane of SC endothelium play a critical role in maintaining the aqueous outflow resistance and homeostatic intraocular pressure (IOP). Because of these factors and their likely role in the development of glaucoma, it is increasingly important to understand the biomechanical landscape of the TM/SC tissues across species and under different conditions. Here we discuss the most recent and relevant studies that have measured TM/SC compliance both in tissues and in cell cultures and their implications for future studies.
Methods: Varying methods have been used to measure the elastic moduli of TM/SC tissues, including atomic force microscopy (AFM), mathematical modeling, and advanced optical coherence tomography (OCT). These are discussed herein. Most of the studies mentioned here were performed on excised tissues, though we also discuss studies in which TM/SC cells are cultured on varying substrates and how this can affect the biomechanical properties of the cells. Stiffness differences were measured between the high- or active-flowing areas of the TM compared with the low- or non-flowing areas. Finally, we report the TM/SC stiffness measurements from animal species that are typically used as model systems to study ocular hypertension and glaucoma.
Results: The elastic modulus as measured by AFM of normal human TM/SC is in the range of approximately
3–7 kPa, whereas the elastic modulus of glaucomatous TM is 20-times stiffer. The elastic modulus of normal human TM/SC tissue that has been perfused at elevated pressure is approximately 1–10 kPa. Mathematical models estimate the elastic modulus of the TM to be 6–128 kPa. The elastic modulus of the TM ranges from 3 kPa in non-human primates and mice, to approximately 1 kPa in rabbits and pigs. TM and SC cells are sensitive to the substrates on which they are grown and often have an increased elastic modulus when treated with glaucomatous stimuli.
Conclusions: The most recent studies discussed herein provide a good framework for better understanding
how the biomechanical properties of the TM/SC can have a direct effect on the proper functioning of the tissue. Ideally, novel methods for measuring TM/SC stiffness in vivo may help with earlier diagnosis and treatment of glaucoma, preventing, or at least delaying, the onset of the disease. These studies may also result in the development and design of more effective therapeutic targets for patients with glaucoma.
Glaucoma Research 2020-2022, pp. 17-24 #2
Edited by: Paul A. Knepper and John R. Samples
© Kugler Publications, Amsterdam, The Netherlands