Selective Laser Trabeculoplasty Mitigates Dexamethasone-Induced Myofibroblast-Like Transformation and Dysfunction in Human Trabecular Meshwork Cells.

PURPOSE: Glucocorticoid-induced glaucoma (GIG) involves trabecular meshwork (TM) fibrosis, including excess extracellular matrix (ECM) deposition and myofibroblast transdifferentiation, which impairs aqueous humor outflow. Selective laser trabeculoplasty (SLT) is an established and effective treatment for lowering intraocular pressure, yet its underlying cellular and molecular mechanisms remain incompletely understood. We investigated whether SLT can normalize the fibrotic phenotype and restore TM cell function in a steroid-treated primary human cell model.

METHODS

Primary human TM cells were exposed to 100 nM dexamethasone (DEX) for 3 or 7 days, then treated with or without SLT (1.0 mJ). ECM proteins (fibronectin, collagen IV) and myofibroblast markers (α-SMA, vimentin, FSP-1) were analyzed by Western blot and immunofluorescence. Migration (scratch, transwell), phagocytosis (fluorescent beads), and proliferation (EdU) were assessed.

RESULTS

DEX induced a flattened, myofibroblast-like morphology, ECM accumulation, and elevated myofibroblast marker expression. SLT markedly reduced these changes, approaching control levels in some cases. DEX-enhanced migration was abolished by SLT in scratch (-110% at 3 d, -95% at 7 d; p < 0.001) and transwell assays (-117% at 3 d, -73% at 7 d; p < 0.0001). SLT partially rescued DEX-impaired phagocytosis (+68% at 3 d; p < 0.01) and proliferation (+37% at 3 d; p < 0.001), with reduced efficacy after prolonged exposure.

CONCLUSIONS

SLT mitigates early glucocorticoid-induced TM fibrosis and restores key cellular functions, supporting its potential as a disease-modifying approach for GIG.