THE EFFECT OF CYTOCHALASIN-D ON OUTFLOW FACILITY AND THE TRABECULAR MESHWORK OF THE HUMAN EYE IN PERFUSION ORGAN-CULTURE

Purpose. To determine the effect of cytochalasin D on outflow facility in the human anterior segment, and the histologic changes that accomp any the effect. Methods. Human anterior segments were studied in perfu sion organ culture. The anterior segment from one eye received cytocha lasin D, and that from the fellow control eye received vehicle; doses ranged from 0.06 mg/ml to 27.7 mg/ml. The duration of action and the e ffect of repeated doses were studied, and the accompanying histologic changes were assessed in 12 pairs of anterior segments. Results. Cytoc halasin D in concentrations of 0.6 mg/ml and 1.1 mg/ml caused increase s in outflow facility of 42% and 37%, respectively (P < 0.05), with a peak effect 2 to 6 hours after infusion and a duration of action of ap proximately 14 hours. Anterior segments were not responsive to repeate d doses (24 hours apart). Compared with the effect of vehicle in contr ol anterior segments, cytochalasin D caused scattered breaks in the in ner wall endothelial lining of Schlemm's canal (4.6 +/- 2.5% versus 0. 7 +/- 0.6%; P = 0.02; anterior segments fixed during maximum drug effe ct). No increase in the amount of optically empty space within the jux tacanalicular tissue was seen. Inner wall breaks persisted, even in ey es in which the outflow facility had returned to baseline; the basemen t membrane and subendothelial matrix of the inner wall remained intact . Final intraocular pressure was inversely correlated with the length of optically empty space immediately adjacent to the inner wall. Concl usions. Cytochalasin D can increase outflow facility in the anterior s egment of the human eye and causes ruptures of the inner wall of Schle mm's canal. These breaks persist, even when interocular pressure retur ns to baseline; the basement membrane and subendothelial matrix of the inner wall appear to remain intact. The final intraocular pressure wa s inversely correlated with the length of optically empty space immedi ately adjacent to the inner wall.