Trabecular meshwork cell differentiation in response to collagen and TGFβ-2 spatial interactions.

Area of Science:

• Biomaterials Science
• Cell Biology
• Ophthalmology

Background:

• Primary open-angle glaucoma (POAG) is a leading global cause of irreversible blindness.
• Current in vitro models struggle to replicate the trabecular meshwork's (TM) complex architecture and cell heterogeneity.
• Understanding trabecular meshwork cell (TMC) phenotype is vital for glaucoma research and therapeutic development.

Purpose of the Study:

• To investigate parameters governing TMC phenotype by adapting extracellular matrix structure.
• To mimic the juxtacanalicular tissue (JCT) region of the TM in vitro.
• To develop advanced in vitro models for studying healthy and pathological TMC states.

Main Methods:

• TMC phenotypic characteristics were analyzed within type I collagen matrices with controlled fiber density and anisotropy, generated via confined plastic compression (PC).
• Biophysical cues from PC-collagen matrices were assessed for their impact on TMC phenotype.
• Localized transforming growth factor-beta 2 (TGFβ-2) exposure was used to induce pathological mesenchymal phenotypes.

Main Results:

• PC-collagen matrices induced JCT-specific TMC characteristics, including elastin and α-β-Crystallin expression, cytoskeletal remodeling, and increased mesenchymal markers.
• TGFβ-2 exposure induced alternative mesenchymal states (fibroblast/smooth muscle or myofibroblast) in TMCs.
• The study successfully generated distinct TMC phenotypic states reflecting both healthy and pathological scenarios.

Conclusions:

• Biophysical cues from the extracellular matrix significantly modulate TMC fate and phenotype.
• The developed in vitro models provide advanced insights into TMC behavior in healthy and POAG-related conditions.
• These models are critical for future pre-clinical testing and understanding glaucoma pathogenesis.