OPTIC-NERVE HYPOPLASIA IN THE FETAL ALCOHOL SYNDROME - A MOUSE MODEL

Optic nerve hypoplasia is commonly observed in children affected by th e fetal alcohol syndrome, and is believed to contribute to their poor visual acuity. We have used a 'binge' model of alcohol abuse in an att empt to recreate this hypoplasia in a mouse model. Pregnant female (C5 7BL/6 x CBA)F-1 mice were injected intraperitoneally with a single dos e of a 25 % solution of ethanol (v:w), either on d 11 or d 12 of gesta tion. Optic nerves were prepared for transmission electron microscopy from offspring at 3, 6, 9 and 15 wk of age (n = 64). A systematic rand om sampling technique was used to analyse both the cross-sectional are as of the optic nerves from semithin sections, and the numbers and cro ss-sectional areas of myelinated axons from thin sections. We found no significant differences either in the cross-sectional area or in the number of axons in the optic nerves between 3 and 9 wk from control an d alcohol-treated groups. From 9 to 15 wk, alcohol-treated groups show ed a loss of approximately 25 % of myelinated axons (65931 +/- 2806-49 186 +/- 3194: mean number of axons +/-S.E.M., respectively). Over the same period the number of axons in control groups was relatively stab le (62087 +/- 2043-64703 +/- 3607). This resulted in an optic nerve wi th statistically significantly fewer myelinated axons at 15 wk in the alcohol-treated group, and was reflected in a trend towards a smaller cross-sectional area of the optic nerve in alcohol-treated groups. Ana lysis of axon calibre distribution within the optic nerves suggested t hat axons of all sizes were lost between 9 and 15 wk in the alcohol-tr eated groups. We suggest a delayed trophic mechanism for this late axo n loss, and that the term optic nerve atrophy may be a more accurate d escription of the process.