Ethacrynic acid increases facility of outflow in the human eye in vitro
L. L. Liang, D. L. Epstein, A. W. de Kater, A. Shahsafaei and K. A. Erickson-Lamy
Howe Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston.
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.
