title: Congenital eye malformations associated with extensive periocular neural crest apoptosis after influenza B virus infection during early embryogenesis.
abstract: OBJECTIVE
  Congenital eye malformations are a leading cause of blindness in children. Influenza virus infections prevail worldwide and have been implicated in congenital defects. Infections acquired during gestation may disrupt eye morphogenesis. We investigated the effects of influenza B virus infection on eye malformations during early embryogenesis.
  
  
  METHODS
  Chick embryos were exposed to influenza B virus at Hamburger-Hamilton stage 9. Maternal infection was conducted by exposing pregnant ICR mice to influenza B virus at the embryonic gestation stage E 5.0. After infection, virus RNA distribution was detected by in situ hybridization at various developmental stages. The distribution of periocular neural crest cells and the extent of apoptosis were examined by immunohistochemical staining, in correlation with eye malformations.
  
  
  RESULTS
  Microphthalmos and anophthalmos, together with neural tube defects, were found in the chick and mouse embryos following the infections. The viral RNA was detected in the head neuroepithelium, optic vesicle, periocular mesenchyme, and the forming ventricles of the developing brain. Immunohistochemical staining revealed aberrant neural crest distribution and extensive apoptosis in the head surface ectoderm, periocular mesenchyme, and optic vesicle in the chick embryos. Furthermore, transplacental infection was confirmed by the presence of viral RNA in the mouse fetuses, with eye and neural tube defects similar to those found in the chick embryos after experimental infections.
  
  
  CONCLUSIONS
  Influenza B virus may act as a teratogen to cause aberrant periocular neural crest cell contribution to eye development and extensive apoptosis, resulting in congenital eye malformations.
authors.affiliation: School of Optometry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Bo-Yie
authors.initials: BY
authors.lastname: Chen
authors.forename: Han-Hsin
authors.initials: HH
authors.lastname: Chang
authors.forename: Shyan-Tang
authors.initials: ST
authors.lastname: Chen
authors.forename: Zih-Jay
authors.initials: ZJ
authors.lastname: Tsao
authors.forename: Shang-Min
authors.initials: SM
authors.lastname: Yeh
authors.forename: Chia-Yung
authors.initials: CY
authors.lastname: Wu
authors.forename: David Pei-Cheng
authors.initials: DP
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D002642:Chick Embryo; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology / Q000821:virology; D047108:Embryonic Development; D005123:Eye / Q000196:embryology / Q000473:pathology / Q000821:virology; D005124:Eye Abnormalities / Q000196:embryology* / Q000473:pathology / Q000821:virology*; D005260:Female; D009981:Influenza B virus / Q000502:physiology*; D008431:Maternal-Fetal Exchange; D008648:Mesoderm / Q000473:pathology / Q000821:virology; D051379:Mice; D009432:Neural Crest / Q000196:embryology / Q000473:pathology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000196:embryology / Q000821:virology*; D011247:Pregnancy; D034443:RNA Transport; D012367:RNA, Viral / Q000378:metabolism
chemical_list: D012367:RNA, Viral