Developmental changes in the optic nerve related to ethanol consumption in pregnant rats: analysis of the ethanol-exposed optic nerve.

Visual impairment is one of the most common ophthalmic abnormalities in fetal alcohol syndrome. Pathologic changes in optic nerve development related to alcohol consumption could be involved in this dysfunction. In order to assess the consequences of pre- and postnatal exposure to alcohol on the developing optic nerve, we administered an ethanol-containing liquid diet (5% w/v) before and during gestation and throughout lactation to rats and their offspring. A group of control animals were kept on a pair-fed isocaloric diet. The optic nerves were obtained at key stages from fetuses (21 days of gestation) and pups (4, 7, 14, 21 and 28 postnatal days). Samples of the optic nerve cross-section, behind the eyeball, were processed for analysis of gliogenesis, myelinogenesis, axonal growth, and remodelling events, using light and electron microscopy. Qualitative, morphometric, and immunocytochemical analyses, alternatively using anti-GFAP and anti-MBP antibodies, were carried out. Optic nerve cross-sections from prenatal and postnatal alcohol-exposed rats showed a decrease in size. Ultrastructural alterations and retarded development in macroglial cells, optic axons, and myelin sheath were also observed. The most prominent abnormalities were: damage of cytoplasmic organelles and disorganization of cytoskeleton in astrocytes; a decrease in free ribosome density and nuclear membrane inclusions in oligodendrocytes; and fragmentation of lamellae, aberrant myelin sheaths and intralamellar inclusions in myelin. These findings suggest that alcohol abuse during pregnancy is teratogenic to the optic nerve and closely related to the altered visual function.