The effect of cytochalasin D on outflow facility and the trabecular meshwork of the human eye in perfusion organ culture.
OBJECTIVE
To determine the effect of cytochalasin D on outflow facility in the human anterior segment, and the histologic changes that accompany the effect.


METHODS
Human anterior segments were studied in perfusion organ culture. The anterior segment from one eye received cytochalasin 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 effect of repeated doses were studied, and the accompanying histologic changes were assessed in 12 pairs of anterior segments.


RESULTS
Cytochalasin D in concentrations of 0.6 mg/ml and 1.1 mg/ml caused increases 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 approximately 14 hours. Anterior segments were not responsive to repeated doses (24 hours apart). Compared with the effect of vehicle in control anterior segments, cytochalasin D caused scattered breaks in the inner 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 effect). No increase in the amount of optically empty space within the juxtacanalicular tissue was seen. Inner wall breaks persisted, even in eyes in which the outflow facility had returned to baseline; the basement 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.


CONCLUSIONS
Cytochalasin D can increase outflow facility in the anterior segment of the human eye and causes ruptures of the inner wall of Schlemm's canal. These breaks persist, even when interocular pressure returns to baseline; the basement membrane and subendothelial matrix of the inner wall appear to remain intact. The final intraocular pressure was inversely correlated with the length of optically empty space immediately adjacent to the inner wall.
Johnson
D H
DH
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.
D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D003571:Cytochalasin B / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects / Q000648:ultrastructure; D005123:Eye / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009924:Organ Culture Techniques; D010477:Perfusion; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D003571:Cytochalasin B