{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:11:48Z","timestamp":1791011508702,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,1,29]],"date-time":"2003-01-29T00:00:00Z","timestamp":1043798400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Time\u2010pregnant mice were treated with 1 mg\/kg dose of RAR antagonist AGN193109 (AGN) on 8 days postcoitum (dpc). Newborn mice and 18\u2010dpc 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\u20102 expression and apoptotic cells in sections of 12\u2010 to 18\u2010dpc embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>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 <jats:italic>AP\u20102<\/jats:italic>\u2013positive cells in ocular tissues on 12, 14, and 18 dpc was significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) reduced in AGN\u2010treated eyes compared to control ones. Additionally, the number of apoptotic cell was significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) increased in AGN\u2010treated eyes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The blocking of RAR function can lead to ocular abnormalities that depict partial phenocopies of vitamin A\u2013deficiency syndrome. Both an inhibition of expression of <jats:italic>AP\u20102<\/jats:italic> and an enhancement of cell death contribute to AGN\u2010induced ocular defects. Birth Defects Research (Part A) 67: 41\u201353, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.10004","type":"journal-article","created":{"date-parts":[[2003,1,30]],"date-time":"2003-01-30T14:04:54Z","timestamp":1043935494000},"page":"41-53","source":"Crossref","is-referenced-by-count":11,"title":["Regulation of AP\u20102 and apoptosis in developing eye in a vitamin A\u2013deficiency model"],"prefix":"10.1002","volume":"67","author":[{"given":"Jian","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devendra 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