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Optic Nerve Hypoplasia in the Fetal Alcohol Syndrome

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In the United States of America, one out of every seven hundred and fifty children is born with fetal alcohol syndrome (FAS). Mothers who consume alcohol anytime during pregnancy, puts their children at risk for multiple constellations of abnormalities when they are born. A common condition observed in children affected is optic nerve hypoplasia, which basically is the underdevelopment of the optic nerve during pregnancy. The affected child has abnormal shaped eyes that appear closer together, which can contribute to the poor visual acuity and their dysmorphic facial features shown up to ninety percent of the births. Unilateral may occur infrequently in one eye and more commonly in both eyes known as bilateral optic disc hyperplasia. Nystagmus is also associated with over half of the affected children. The optic nerve head is relatively smaller in affected children, then in a normal child. Axons are neurons that form the optic nerve and are myelinated. Since there is a loss of axons in the nerve during optic nerve hypoplasia (ONH), it compensates for the loss of retinal ganglion cells. A lot of the visual disabilities results are located on the retinal ganglion cells when alcohol affects the nervous system. In order to develop a model for optic nerve hypoplasia, researchers used mice as a model for alcohol treated animals instead of humans.

Ethanol is injected into the mice during a period of time where the forebrain target tissues and the retinal ganglion cells are undergoing cell division and the axons are grown into the optic stalk. This period is called gestation, which can appear on day eleven or day twelve. Throughout this experiment the size of the optic nerve, and the calibre and number of myelinated axon cells present is measured.

In order for the mice to become pregnant they were mated overnight. Twenty five percent of ethanol is injected into the pregnant female mice and a control mouse is injected with saline at the same time during gestation. The optic nerves where dissected out at three, six, nine and fifteen weeks apart. However, the nerves are observed overnight in fresh fixative. Also, some of the semithin sections were cut from the middle of each optic nerve. Since two to three hundred axons to count are present on each nerve, their cross-sectional areas were measured. Finally, in the experiment, the blood alcohol levels were tested and measured to see the different reactions of mice under the influence of alcohol, intoxicated, and the treated with salt, control mice.

From about fifteen minutes to two hours after the mice were injected with alcohol, they were stationary and inebriated. A normal human blood alcohol blood level that is lethal range between three hundred and eight hundred percentage milligrams, but within five minutes the mice blood alcohol levels peak was at four hundred to four hundred and fifty percent milligrams and they did not become negligible again until six hours later. If you refer to Figure 1 in the article, it shows an exponential curve fit that gives you a view of how the blood alcohol levels decreased over a period of time. Also from this model, a decrease in the cross-sectional areas of the right optic nerve in the mice injected with alcohol is observed. On the eleventh and twelfth day of gestation, there is no significant change seen in the ethanol-treated mice or the control group mice. However, after a couple of weeks begin to pass, the control nerves increased. In the fifteenth week, the treated mice decreased in their cross-sectional areas in the optic nerve of the baby, which is the exact opposite of how the control mice continued to increase, shown in Figure 2. To estimate nerve fibers and the size of myelinated axons present the sampling method presented by Mayhem in 1990 is used. It is important to realize that forty percent of the retinal ganglion cells are lost during the early postnatal period automatically, so we can conclude that as time pass only a few unmyelinated axons are still present. Once again there was still no major difference shown in the mice. However, according to Figure 3, between weeks nine and fifteen the control mice had twenty-five more percent control nerves than the affected mice because the number of myelinated axons of the cross-sectional areas decreased. Although the histograms show that the results observed over the weeks were similar, there is still different reactions' happening over this period of time. For example, in the first six weeks more small axons is present in the alcohol treated groups compared to the control groups and the diameter became



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