{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:15:47Z","timestamp":1760577347617},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,17]],"date-time":"2014-03-17T00:00:00Z","timestamp":1395014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over\u2010exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of <jats:styled-content style=\"fixed-case\">HNK<\/jats:styled-content>\u20101<jats:sup>+<\/jats:sup> cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti\u2010oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> production and perturbs Pax6 expression.<\/jats:p>","DOI":"10.1111\/jcmm.12260","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T06:20:02Z","timestamp":1395123602000},"page":"1134-1143","source":"Crossref","is-referenced-by-count":23,"title":["Excess caffeine exposure impairs eye development during chick embryogenesis"],"prefix":"10.1111","volume":"18","author":[{"given":"Zheng\u2010lai","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Histology &amp; Embryology Key Laboratory for Regenerative Medicine of the Ministry of Education Institute of Fetal\u2010Preterm Labor Medicine Medical College of Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Histology &amp; Embryology Key Laboratory for Regenerative Medicine of the Ministry of Education Institute of Fetal\u2010Preterm Labor Medicine Medical College of Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Histology &amp; Embryology Key Laboratory for Regenerative Medicine of the Ministry of Education Institute of Fetal\u2010Preterm Labor Medicine Medical College of Jinan University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manli","family":"Chuai","sequence":"additional","affiliation":[{"name":"Division of Cell and Developmental Biology University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products Jinan University Guangzhou 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