title: Histological characterisation of the ethanol-induced microphthalmia phenotype in a chick embryo model system.
abstract: The eye is a sensitive indicator of the teratogenic effects of ethanol with ophthalmic defects such as microphthalmia frequently observed in FAS children. In this study, we have optimised the chick-embryo model system to investigate ethanol-induced ocular defects. Injection of 20% ethanol (125μl) directly into the yolk sac of HH-stage 7 embryos resulted in an overall 30% incidence of eye anomalies including microphthalmia. Ocular measurements showed that this treatment regime caused a significant reduction in overall globe size. Histological examination of microphthalmic specimens revealed three subgroups: (1) all ocular structures developed but were significantly retarded compared to age matched controls, (2) the bi-layered optic cup developed but with no evidence of lens induction, and (3) the optic vesicle failed to invaginate but remained as a vesicular structure comprising of a single layer of retinal pigment cells with no evidence of a neuro-retinal cell layer or lens structure. Further analysis identified clusters of apoptotic bodies in the ventral telencephalon, a region responsible for the expression of important genes in ocular specification. These results support a growing body of evidence, indicating that ethanol targets inductive signals in early eye development involving lens formation and retinal ganglion cell differentiation. The possible involvement of Shh, Fgf8, Bmp4 and Pax6 is discussed in relation to these outcomes.
authors.affiliation: School of Medicine and Medical Science, Health Sciences Building, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kennelly
authors.forename: Deirdre
authors.initials: D
authors.lastname: Brennan
authors.forename: Kushal
authors.initials: K
authors.lastname: Chummun
authors.forename: Seamus
authors.initials: S
authors.lastname: Giles
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005123:Eye / Q000196:embryology / Q000473:pathology; D008850:Microphthalmos / Q000139:chemically induced / Q000196:embryology / Q000473:pathology; D009929:Organ Size; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D013723:Teratogens; D000431:Ethanol