Retinal structure and function in monkeys with fetal alcohol exposure.

Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive. We recently reported that fetal alcohol exposure (FAE) in vervet monkeys induces anomalies of full-field electroretinogram (ERG) waveforms that suggest premature aging of the retina. The goal of this study is to characterize the anatomo-functional mechanisms underlying the retinal changes observed in fetal alcohol exposed (FAE) monkeys, and age- and sex-matched normals. First, we examined in vivo the fundus of the eyes, measured intraocular pressure (IOP) and assessed cone activity using flicker ERG. Second, we investigated ex vivo, protein expression and anatomical organization of the retina using Western blotting, classical histology and immunohistochemistry. Our results indicated that the fundus of the eyes showed both, increased vascularization (tessellated fundus) and IOP in FAE monkeys. Furthermore, light-adapted flicker responses above 15 Hz were also significantly higher in FAE monkeys. Although there were no obvious changes in the overall anatomy in the FAE retina, Glial Fibrillary Acidic Protein (GFAP, a potent marker of astrocytes) immunoreactivity was increased in the FAE retinal ganglion cell layer indicating a strong astrogliosis. These alterations were present in juvenile (2 years old) monkeys and persist in adults (8 years old). Moreover, using specific cell type markers, no significant modifications in the morphology of the photoreceptors, horizontal cells, bipolar cells, and amacrine cells were observed. Our data indicate that FAE does indeed induce anatomical changes within the retinal ganglion cell layer that are reflected in the increased photosensitivity of the cone photoreceptors.