Congenital eye malformations associated with extensive periocular neural crest apoptosis after influenza B virus infection during early embryogenesis

[摘要] Purpose: Congenital eye malformationsare a leading cause of blindness in children. Influenza virusinfections prevail worldwide and have been implicated in congenitaldefects. Infections acquired during gestation may disrupt eyemorphogenesis. We investigated the effects of influenza B virusinfection on eye malformations during early embryogenesis. Methods: Chick embryos were exposed toinfluenza B virus at Hamburger-Hamilton stage 9. Maternal infection wasconducted by exposing pregnant ICR mice to influenza B virus at theembryonic gestation stage E 5.0. After infection, virus RNAdistribution was detected by in situ hybridization at variousdevelopmental stages. The distribution of periocular neural crest cellsand the extent of apoptosis were examined by immunohistochemicalstaining, in correlation with eye malformations. Results: Microphthalmos andanophthalmos, together with neural tube defects, were found in thechick and mouse embryos following the infections. The viral RNA wasdetected in the head neuroepithelium, optic vesicle, periocularmesenchyme, and the forming ventricles of the developing brain.Immunohistochemical staining revealed aberrant neural crestdistribution 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 ofviral RNA in the mouse fetuses, with eye and neural tube defectssimilar to those found in the chick embryos after experimentalinfections. Conclusions: Influenza B virus may actas a teratogen to cause aberrant periocular neural crest cellcontribution to eye development and extensive apoptosis, resulting incongenital eye malformations.

[学科分类] 生物化学/生物物理