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Huiyi chen, Paul S. Sander, Arghavan Almony, Lixing W. Reneker; Ocular Abnormalities In A Mouse Model of Fetal Alcohol Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4926.
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Fetal alcohol syndrome (FAS) refers to a pattern of mental and physical defects that can develop in a fetus due to maternal alcohol consumption. FAS is the leading cause of intellectual disability in the Western world. Ocular abnormalities are present in about 90% of FAS cases. Two common ocular abnormalities in FAS are coloboma and microphthalmia. At present the pathogenesis of these abnormalities is not entirely clear. Using a mouse model of FAS, we investigated the pathogenic mechanisms of coloboma and microphthalmia induced by alcohol exposure during pregnancy.
On embryonic day 7.5 (E7.5), the pregnant C57BL/6J female mice were injected intraperitoneally twice at an interval of 4 hours with 25% ethanol at a dose of 0.015 mL/gm body weight. Ocular defects at E12.5 or E13.5 were evaluated under a dissecting microscope and then processed for histological analysis including H&E staining, immunofluorescence and TUNEL assay.
Based on the size of the eye and formation of retinal pigment epithelium (RPE) pigmentation, the embryos isolated from the alcohol-exposed mothers were categorized into 3 groups: normal, moderately and severely affected. The eyes in the severely affected group demonstrated significant coloboma and microphthalmia. In this group, the RPE differentiation near the optic fissure area was either delayed or defective when compared to the normal eyes. In the severely affected eyes, apoptosis was increased in the RPE layer but not in the neural retina. Additional defects in these eyes include formation of a much smaller lens vesicle often connected to the cornea with a lens stalk, a key feature of Peters’ anomaly in humans.
Coloboma in FAS maybe caused by defective RPE differentiation at the optic fissure region and increase of apoptosis in the RPE. Microphthalmia in FAS may be a result of combined abnormal formation of optic cup and lens vesicle during early eye development.
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