| First Author | Zhou J | Year | 2003 |
| Journal | Birth Defects Res A Clin Mol Teratol | Volume | 67 |
| Issue | 1 | Pages | 41-53 |
| PubMed ID | 12749383 | Mgi Jnum | J:84140 |
| Mgi Id | MGI:2665262 | Doi | 10.1002/bdra.10004 |
| Citation | Zhou J, et al. (2003) Regulation of AP-2 and apoptosis in developing eye in a vitamin A-deficiency model. Birth Defects Res Part A Clin Mol Teratol 67(1):41-53 |
| abstractText | BACKGROUND: Eye malformations induced by vitamin A deficiency (VAD) during pregnancy is a major part of the VAD syndrome. But the signaling role of retinoic acid (RA) in ocular tissues is poorly understood. The goal of this study was to determine the role of retinoic acid receptor (RAR) in the development of eye and the possible signaling pathway. METHODS: Time-pregnant mice were treated with 1 mg/kg dose of RAR antagonist AGN193109 (AGN) on 8 days postcoitum (dpc). Newborn mice and 18-dpc embryos were used for phenotype studies. Embryonic eyes of 18 dpc were sectioned for histological study. With immunohistochemistry and TUNEL method, we monitored the alternation of AP-2 expression and apoptotic cells in sections of 12- to 18-dpc embryos. RESULTS: Treatment with AGN resulted in severe craniofacial and eye malformations in virtually all exposed fetuses. The ocular abnormalities included severe defects in anterior segments such as focal corneal thickening and eversion, absence of corneal endothelium and anterior chamber, differentiation defects of lens, as well as defects in posterior segment such as persistent hyperplastic primary vitreous and retinal eversions. The percentage of AP-2-positive cells in ocular tissues on 12, 14, and 18 dpc was significantly (P < 0.05) reduced in AGN-treated eyes compared to control ones. Additionally, the number of apoptotic cell was significantly (P < 0.05) increased in AGN-treated eyes. CONCLUSIONS: The blocking of RAR function can lead to ocular abnormalities that depict partial phenocopies of vitamin A-deficiency syndrome. Both an inhibition of expression of AP-2 and an enhancement of cell death contribute to AGN-induced ocular defects. |
