Characterization of extracellular matrix deposited by segmental trabecular meshwork cells

Area of Science:

• Ocular biomechanics
• Extracellular matrix biology
• Glaucoma pathobiology

Background:

• Extracellular matrix (ECM) properties influence cell behavior in health and disease.
• Glaucoma involves trabecular meshwork (TM) stiffening and segmental matrisome changes, impacting aqueous humor outflow.
• Current models lack the ability to investigate the segmental nature of TM matrix alterations.

Approach:

• Characterized biomechanical attributes, matrisome composition, and crosslink incidence in TM cells from high- and low-flow regions.
• Investigated the impact of glucocorticosteroid treatment on TM cell-deposited matrix.
• Utilized primary TM cells for in vitro modeling.

Key Points:

• Matrix deposited by low-flow TM cells is stiffer and has more immature and mature crosslinks compared to high-flow cells.
• Glucocorticosteroid treatment exacerbates matrix stiffening and crosslinking in low-flow TM cells.
• TM cells from high- and low-flow regions exhibit differential responses to glucocorticosteroids in their matrix composition.

Conclusions:

• The study provides insights into the segmental differences in TM matrix properties relevant to glaucoma.
• While the mechanistic basis for matrix stiffness remains to be determined, the model is valuable for studying TM pathobiology.
• Understanding these matrix alterations is crucial for developing targeted glaucoma therapies.