Ethacrynic acid increases facility of outflow in the human eye in vitro

Anterior segments of human donor eyes were perfused with culture medium at a perfusion pressure of 15 mm Hg in a 5% carbon dioxide environment at 37 degrees C. After determination of a baseline facility of outflow, the perfusion chamber contents were exchanged with either drug vehicle or ethacrynic acid, at concentrations ranging from 0.01 to 0.25 mmol/L, after which postdrug facility was measured in the continuous presence of drug vehicle or ethacrynic acid. Ethacrynic acid increased facility of outflow from 28% to 105% at ethacrynic acid concentrations of 0.01 to 0.25 mmol/L, respectively. No morphologic correlate of the facility increase was observed with 0.01-mmol/L ethacrynic acid, nor were there any signs of cellular toxic effects. At 0.1 mmol/L, separations between trabecular meshwork cells and breaks between inner-wall cells were observed. At 0.25 mmol/L, focal areas of cell swelling and necrosis were noted. This study demonstrated that ethacrynic acid increases outflow facility in the aged human eye at concentrations that produce no apparent toxic effects. Therefore, ethacrynic acid may potentially prove useful in the treatment of glaucoma.