From Load-Bearing Tissue to Failed Filter: A Conceptual Framework for Trabecular Meshwork Breakdown in...

Area of Science:

• Ophthalmology
• Glaucoma Research
• Biomaterials Science

Background:

• Pseudoexfoliation glaucoma (PXG) presents a more severe clinical course and higher intraocular pressure (IOP) than primary open-angle glaucoma (POAG).
• PXG pathogenesis involves pseudoexfoliation (PXF) fibrillar material deposition, leading to progressive structural failure of the trabecular meshwork (TM).
• The TM, crucial for IOP regulation, is significantly impacted by PXF material and extracellular matrix (ECM) dysregulation in PXG.

Purpose of the Study:

• To elucidate the mechanisms of trabecular dysfunction in PXG.
• To integrate evidence from TM biology, PXF material science, and glaucoma pathophysiology.
• To propose a novel five-stage framework for TM failure in PXG.

Main Methods:

• Narrative review of existing literature.
• Amalgamation of data from TM biology, PXF material science, and glaucoma pathophysiology.
• Synthesis of evidence to develop a conceptual framework.

Main Results:

• The review consolidates understanding of TM dysfunction in PXG.
• A five-stage framework for TM failure in PXG is proposed.
• Both mechanical obstruction and ischemic/oxidative stress are implicated in TM dysfunction.

Conclusions:

• The proposed framework offers a structured understanding of TM failure in PXG.
• Further research into the proposed stages may reveal new therapeutic targets.
• Distinguishing PXG from POAG pathogenically is crucial for targeted treatment.