[Developmental mechanisms of congenital eye abnormalities]

Experimental teratology in mice was studied to clarify the developmental mechanisms of congenital eye abnormalities. Pregnant Jcl: ICR mice were treated intraperitoneally with ochratoxin A on day 7 of pregnancy. The offspring were grossly observed on day 9, 10, 11, 12, 13, 14, 16 or 18 of gestation, or at the second or fourth week after birth. Then, the eyes were histologically examined in serial sections. Mother mice were injected with ochratoxin A on day 8, 9, 10 or 11 of pregnancy, and the eyes of fetuses were examined on day 16 of gestation to determine the critical periods for the congenital eye abnormalities. Pregnant C57BL/6NJcl mice were also given an intraperitoneal injection of ochratoxin A on day 7 of pregnancy, and the eyes of offspring were observed grossly and histologically on day 16 or 18 of gestation, or at the second or fourth week after birth. Fetal and postnatal eyes showed various kinds and degrees of developmental abnormalities histologically. They included anophthalmia, microphthalmia, aphakia, mesenchymal dysgenesis of the anterior segment, faulty separation of the lens vesicle, developmental abnormalities of the vitreous, faulty closure of the embryonic fissure, retinal rosette formation and aberrant optic nerve fiber. Since anophthalmia, microphthalmia and aphakia caused by the developmental disturbances of the optic and lens vesicles were not established in the fetuses whose mothers were treated with ochratoxin A after day 9 of pregnancy, the critical periods for these abnormalities were considered to be on day 8 of gestation or earlier. Mesenchymal dysgenesis of the anterior segment, faulty separation of the lens vesicle and developmental abnormalities of the vitreous were frequently observed in the fetuses whose mothers were injected with ochratoxin A on day 7, 8 or 9 of pregnancy. It was considered that there was a correlation between the critical periods for these three abnormalities and the stage of the neural crest cell migration around the optic vesicle. Mesenchymal dysgenesis of the anterior segment observed in mice corresponded to the Axenfeld-Rieger syndrome or Peters' anomaly encountered clinically. Processes of production of these abnormalities based on the faulty migration of the neural crest cells which form the ocular anterior segment were demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)