Effect of epinephrine in vitro on the morphology, phagocytosis, and mitotic activity of human trabecular endothelium.

Epinephrine exerts a direct effect on cell morphology, phagocytosis and mitotic activity of human trabecular endothelium in primary culture. Its action is probably mediated through both beta and alpha adrenoceptors in a dose-time dependent manner. Younger cells and cells that were loosely attached to the substrate were found to be affected more rapidly and severely than were older cells and those in confluent regions where cell-to-cell attachment and stress fibers were well established. Continuous exposure to epinephrine at a concentration of 10(-5) M led to cessation of the normal cytokinetic cell movements, inhibition of mitotic and phagocytic activity, marked cell retraction, separation from the substrate, and, by 4-5 days, degeneration of cells. Similar, but less marked changes were seen with a concentration of 10(-6) M, the cell degeneration becoming apparent after one week of exposure. A still weaker concentration of epinephrine, 10(-7) M, did not result in cell degeneration even after 10 days of exposure and observation. On complete withdrawal of the drug, the cellular effects were reversible even after 3 days' exposure to 10(-5) M and 5-7 days' exposure to 10(-6) M epinephrine. The action of epinephrine was partially blocked by pretreatment of cultured trabecular cells with the beta-blocker, timolol. Available evidence suggests that the mechanism of action of epinephrine is mediated through both beta and alpha adrenoceptors, and that it intimately involves the cytoskeletal system of the cells. Extrapolation of our findings in vitro suggests that use of maximal doses of epinephrine over a prolonged time may contribute to tissue damage in certain conditions of glaucoma.