Dexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and Matrix.

Area of Science:

• Ophthalmology
• Biophysics
• Cell Biology

Background:

• Corticosteroids can cause ocular hypertension and steroid-induced glaucoma.
• The biomechanical changes in trabecular meshwork (TM) cells and extracellular matrix (ECM) contributing to this are not well understood.

Purpose of the Study:

• To investigate the biomechanical effects of dexamethasone (DEX) on human TM (HTM) cells and ECM.
• To determine the in vivo biomechanical changes in rabbit TM after DEX treatment.

Main Methods:

• Cultured primary human TM (HTM) cells with or without DEX for 3 days or 4 weeks to assess cell and matrix mechanics and proteomics.
• Treated adult rabbits with topical 0.1% DEX or vehicle for 3 weeks to measure TM mechanics.

Main Results:

• DEX treatment increased HTM cell stiffness 2-fold, associated with ERK1/2 activation and αSMA overexpression.
• DEX-treated HTM cells deposited stiffer, more organized ECM with elevated glaucoma-associated proteins.
• Rabbit TM stiffness increased 3.5-fold after DEX treatment.

Conclusions:

• DEX increases TM cell stiffness, activates MAPK pathways, and stiffens ECM in vitro.
• DEX treatment leads to increased TM tissue stiffness in vivo.
• Glucocorticoid treatment initiates biophysical alterations contributing to increased intraocular pressure (IOP).