Optic vesicle defects induced by vincristine sulfate: an in vivo and in vitro study in the mouse embryo.

Abstract

The optic vesicle develops from cuboidal neuroepithelial cells which become high-columnar, then become wedge-shaped. Vincristine sulfate, a microtubule inhibitor, was used to study the role of microtubules in optic vesicle formation. Swiss-Webster mice were injected with vincristine sulfate on the eighth day of gestation, placebo females received an equivalent volume of saline, and additional females were not injected. All embryos were harvested on the 10th day of gestation. Additional embryos were cultured by the whole embryo culture technique described by New et al. ('73) beginning on the ninth day of gestation for 24 hours. When embryos were harvested on the 10th day of gestation, crown-rump lengths, developmental stage, and the number of visible anomalies were recorded. Embryos were then examined using light, transmission, and scanning electron microscopy. Embryos exposed to vincristine sulfate in vivo or in vitro were significantly smaller and developmentally delayed when compared to the control groups. The embryos treated in vivo appeared to be more severely affected than those exposed in vitro. Observed malformations were similar in both experimental groups, and consisted mainly of closure defects of the cephalic neural folds and defective formation of the optic vesicles. The optic vesicle defects ranged from complete absence to asymmetrical development. Microtubules appeared to be disorganized, S-shaped, or incorporated into paracrystalline inclusion structures.