Latrunculin B effects on trabecular meshwork and corneal endothelial morphology in monkeys.
To determine the mechanism of latrunculin B (LAT-B)-induced decrease in outflow resistance and the effect of LAT-B on the cornea, structural changes of the trabecular meshwork (TM) and the corneal endothelium following LAT-B were studied in the live monkey eye. LAT-B (0.5 microM) and vehicle were administered by anterior chamber exchange and infusion with cationized and non-cationized gold solution in opposite eyes. The eyes were fixed by infusing Ito's solution and enucleated. Anterior segments were quadrisected and embedded in Epon-Embed 812. Morphology of the TM and the corneal endothelium was studied by light and electron microscopy. LAT-B-induced morphological changes in the TM included: (1) loss of microfilament integrity in cells, especially in TM cells on the collagen beams; (2) development of numerous cytoplasmic projections of the sub-canalicular cells (SUB); (3) reorganization of intermediate filaments in Schlemm's canal inner wall (IW) cells; (4) massive 'ballooning' of the juxtacanalicular (JXT) region, leading to a substantial expansion of the space between the IW of Schlemm's canal and the trabecular collagen beams; and (5) retention of extracellular matrix (ECM), trapped between the SUB cell layer and IW cells. No detrimental effects on tight junctions, giant vacuoles, and cell-cell and cell-ECM adhesions were observed. Endocytosis of gold particles was not affected. Morphology of the corneal endothelium of the LAT-B-treated eye was unchanged. In conclusion, TM changes in the LAT-B-treated eye suggest that the expansion of the JXT space may account for the decrease in outflow resistance induced by latrunculins. The outflow-effective concentration of LAT-B administered intracamerally does not significantly affect the corneal endothelium.
Sabanay
Ilana
I
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Tian
Baohe
B
Gabelt
B'Ann T
BT
Geiger
Benjamin
B
Kaufman
Paul L
PL
D000199:Actins / Q000648:ultrastructure; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure; D007429:Intraocular Pressure / Q000187:drug effects; D008252:Macaca fascicularis; D008387:Marine Toxins / Q000494:pharmacology*; D008854:Microscopy, Electron; D011161:Porifera; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000648:ultrastructure
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008387:Marine Toxins; D013844:Thiazoles; D053778:Thiazolidines; C037068:latrunculin B