Abstract
Abstract: :
Purpose: To determine the mechanism of latrunculin B (Lat–B)–induced outflow resistance decrease, and the effect of Lat–B on the corneal endothelium, in the live monkey eye. Methods: Fluid outflow was measured by perfusion of the anterior chamber with cationized and non–cationized gold solution ± 0.5µM Lat–B in opposite eyes. The eyes were fixed by infusing Ito's solution and enucleated. Anterior segments were quadrisected, immersion–fixed and embedded in Epon–812. Morphologies of the trabecular meshwork (TM) and the corneal endothelium were studied by light and electron microscopy. Results: Lat–B (0.5µM) affected TM organization and increased fluid outflow. Morphological changes in the TM included: (1) loss of microfilament integrity in cells especially in TM cells on the beams; (2) development of numerous cytoplasmic projections of the sub–canalicular cells, similar to those formed in a wide variety of cultured cells; (3) loss or reorganization of intermediate filaments in Schlemm's canal inner wall (IW) cells; (4) a 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–canalicular cell layer and IW cells. No significant effects on tight junctions, giant vacuoles, and cell–cell and cell–ECM adhesions were observed. Morphology of the corneal endothelium of the Lat–B–treated eye was essentially unchanged. Conclusions:TM changes in the Lat–B–treated eye suggest that the expansion of the JXT space may account for the outflow resistance decrease induced by latrunculins. The outflow–effective concentration of Lat–B administered intracamerally does not significantly affect the corneal endothelium.
Keywords: outflow: trabecular meshwork • cytoskeleton • cornea: endothelium