Developmental eye abnormalities in mouse fetuses induced by retinoic acid

To clarify the relationship between neural crest cells and various developmental eye abnormalities, pregnant mice were administered an intraperitoneal injection of 12.5 mg/kg retinoic acid (RA) suspended in corn oil on day 7 of pregnancy (RA group). Control mice received an equal volume of corn oil only (control group). The fetuses were removed by laparotomy on day 18 of gestation. The fetal mortality was 46.3% in the RA group and 2.2% in the control group. The live fetuses in both groups were observed grossly, and the eyes were examined histologically in serial sections. In the RA group, gross malformations were observed, including microphthalmos (95.5%), cleft lip and palate (36.4%), and central nervous system anomalies (31.8%). In the control group, these malformations were seen in only 6.7%, 0%, and 2.2%, respectively. Histologic examinations in the RA group revealed microphthalmos (47.7%), anophthalmos (38.6%), faulty closure of the embryonic fissure (36.4%), developmental abnormalities of the vitreous (34.1%), aphakia (22.7%), goniodysgenesis (18.2%), and faulty separation of the lens vesicle (15.9%). They were detected in only 3.3%, 1.1%, 3.3%, 8.9%, 1.l%, 2.2%, and 2.2%, respectively, of the control group. These developmental eye abnormalities arose from abnormal migration of neural crest cells.