Malformations of the eye in rat fetuses caused by vincristine and their abnormal morphogenesis

Abstract

Wister rats were treated with a single intraperitoneal injection of 0.2mg/kg of vincristine of day 8 of pregnancy, and the fatuses were examined externally on day 20. Major malformations were as follows: Anophthalmos and microphthaomos were 44.10%, malformations of the CNS were 45.13%, and those of the face were 48.21%. On malformations of the eye, bilateral cases were 66.28% and unilateral ones were 33. 72%. Malformed eyes on the right side were 47.55%, and those on the left side were 52.45%. Incidence of anophthalmos was 53.85%, that of microphthalmos was 45.45%. Besides, there were open eyelids, 6.29%. When they were examined histologically, almost all cases grossly diagnosed as anophthalmos were proved to be microphthalmos which had some components of the eye cup. Under a microscope, there were found few complete anophthalmos, many microphthalmoses of extreme degree, "some with complicated retinal foldings, few with slight coloboma of the retina, etc. Another series of experiments were dynamic studies of the abnormal morphogenesis of the eye. Embryos were examined on day 10, i. e. , two days after the treatment; thereafter they were taken out every 24 hours until day 19. These were examined histologically. A11 cases examined on day 10 had the eye vesicle. Even those with intense cranioschisis also had the eye vesicle. However, on day 11 when the eye vesicle develops into the eye cup, the process of the development was arrested or involved in an abnormal condition. When embryos were examined on day 12, the eye cup was small in size suggesting sequential microphthalmos. Of those examined of day 13, there were cases suggesting initial involvement which would lead to anophthalmos. In such cases, only rudiments of the eye cup were detected. On the later stages of the development, i. E., after day 13, besides cases of the above mentioned abnormal conditions, absence of the optic nerve and sometimes malformations of the diencephalon were associated. In the above results, a spectrum of malformations of the eye was observed such as from a complete anophthalmos to a slight coloboma of the retina. However, these malformations of the eye induced by vincristine were generally similar to those produced by other extrinsic factors. All cases of anophthalmoses were degenerative anophthalmoses, and no cases of primary anoththalmos were found.