Congenital eye malformations associated with extensive periocular neural crest apoptosis after influenza B virus infection during early embryogenesis.
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.
Chen
Bo-Yie
BY
School of Optometry, Chung Shan Medical University, Taichung, Taiwan.
Chang
Han-Hsin
HH
Chen
Shyan-Tang
ST
Tsao
Zih-Jay
ZJ
Yeh
Shang-Min
SM
Wu
Chia-Yung
CY
Lin
David Pei-Cheng
DP
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
D012367:RNA, Viral