Critical Period for Retinoic Acid-induced Developmental Abnormalities of the Vitreous in Mouse Fetuses

Abstract

To elucidate the underlying developmental mechanisms of persistent hyperplastic primary vitreous (PHPV) in humans, we investigated a mouse model for PHPV induced by retinoic acid. We treated C57BL/6NJcl mice at various stages of pregnancy (gestation days 7, 8, 9, 10, 11, or 12) with the teratogen retinoic acid, which affects the migration of neural crest cells. Untreated pregnant mice served as a control group. The eyes of the fetuses were examined histologically on day 18 on gestation. Developmental abnormalities of the vitreous were defined as the presence of excessive mesenchymal tissue in the vitreous cavity. The incidence of developmental abnormalities of the vitreous in all groups, except for those treated on day 12 of pregnancy, significantly exceeded that in the control group (P<0.01). The histological characteristics of the observed vitreous abnormalities in mice resembled those found in PHPV clinically. Retinoic acid-induced abnormalities in mice can serve as an experimental model for PHPV by environmental factors. Results suggest that the critical period for these retinoic acid-induced abnormalities was during days 7 to 11 of gestation, which corresponds to a critical period of 2.5 to 7 weeks of gestation for PHPV in humans.