The prenatal development of the optic fissure in colobomatous microphthalmia.

The coloboma in the cinnamon mouse homozygous for the microphthalmia gene is caused when optic fissure closure, which normally occurs between the 11th and the 13th gestational day, does not occur. This study sought to determine the cause of this fusion failure, and to identify any foci of fusion that occur later in gestation. Microphthalmic fetuses from the 11th-20th gestational day were obtained by datemating cinnamon mice heterozygous for the microphthalmia gene. Coronal serial sections of the eyes were examined at light and electron microscopy. Initially, the fissure margins became apposed only in the posterior aspects of the eye. A failure of basement membrane disintegration at the fissure margins prevented fusion at the 12th and 13th days. On the 14th day, small foci of basement membrane disintegration were identified in the area of the developing optic disc. Although the fusion zone enlarged later in gestation, it was limited to the area of the optic disc and showed that the two retinal layers did not separate. This study has shown that abnormal growth and invagination lead to delayed apposition of the optic fissure margins. These features together with a failure of basement membrane disintegration appear to be the main factors involved in coloboma formation. It is suggested that the excessive number of outer-layer cells that are inverted into the fissure, as well as abnormal or reduced numbers of phagocytic cells, may affect the persistence of the basement membrane. Alternatively, a primary defect of the pigment epithelial cell may lead to the development of the hypercellular and nonpigmented outer layer associated with the lack of basement membrane disintegration and nonfusion in this mutant.