MICROTUBULE DISRUPTION LEADS TO CELLULAR CONTRACTION IN HUMAN TRABECULAR MESHWORK CELLS

PURPOSE. To determine whether microtubule- and actin-altering drugs, w hich have been shown to increase aqueous humor outflow, cause cellular contraction in human trabecular meshwork (HTM) cells. METHODS. HTM ce lls were plated in culture dishes containing a polymerized deformable silicone substrate. After 48 hours, the dishes were placed on an inver ted microscope and treated with ethacrynic acid, colchicine, vinblasti ne, cytochalasin B, or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and then recorded on videotape for 15 minutes. An increase in si licone substrate wrinkle size and/or number indicated a contraction. S ham controls were used. RESULTS. Cellular contraction was observed wit h ethacrynic acid, colchicine, and vinblastine in the 10(-5) to 10(-4) M dosage range. Pretreatment with H-7 blocked these effects. Cytochal asin B did not produce cellular contraction. CONCLUSIONS. Microtubule disruption causes cellular contraction in HTM cells, and this effect d epends on an intact actin cytoskeleton network. Contraction of trabecu lar meshwork cells in response to various stimuli is an attractive hyp othesis for possible homeostatic mechanisms in the outflow pathway, an d this may serve as a focus for novel glaucoma drug development.