Electroretinographic studies in an animal model of fetal alcohol syndrome

It has been established beyond reasonable doubt that prenatal ethanol exposure is teratogenic to the developing fetus. Infants born to alcoholic women are frequently diagnosed as having the Fetal Alcohol Syndrome (FAS), which is primarily characterized by reduced birth and brain weight, a significant degree of mental retardation, and specific craniofacial dysmorphogenesis. The craniofacial anomalies include ocular manifestations such as microphthalmia, strabismus, epiphakia and amblyopia. These adverse effects of prenatal ethanol exposure on the anatomical development of the eye are well documented, however, its effect on the physiological function of the retina is unknown. The purpose of the present study was to identify and characterize functional retinal alterations resulting from ethanol exposure during the prenatal developmental period. Specifically, the objectives were to develop an animal (Rat) model of FAS, and to measure, using the electroretinogram (ERG), amplitude intensity functions (V-log I), temporal response functions, and adaptation functions under varying background levels of illumination. Single flash ERGs were measured under dark-adapted (DA) and light- adapted (LA) conditions, in the female offspring of Long-Evans hooded rats. One group was exposed to ethanol (ETOH 1) only during pregnancy, while a second group was exposed over an additional 10 day postnatal period (ETOH 2). Compared to controls the treatment offspring had reduced birth and organ weights, altered organ/body weight ratios and microphthalmia- all of these effects are indicators of FAS. During development these offspring continued to exhibit retarded growth. Under DA conditions, rod ERGs showed (i) a 1-log-unit increase in the absolute threshold for the b-wave in ETOH 1 and ETOH 2, (ii) an exposure-related decrease in the maximum amplitude of the a- and b-wave and (iii) an increase in the a-wave and b-wave latency only in ETOH 2. Under LA conditions, decreases in the b-wave V-Iog I function occurred all at background intensities, resulting in a non-uniform response compression. Increment-threshold functions were decreased at the dimmest background intensity using a low amplitude criterion, while using a higher criterion revealed an exposure-response decrease in sensitivity at the three lowest background intensities used. In addition, the prenatal ethanol exposure caused an altered sensitivity of DA following a bleach and depressed amplitude-recovery functions of the b-wave. However, no effect on the critical flicker frequency was observed. It is concluded that in utero ethanol exposure produced alterations in retinal adaptive mechanisms, "gain" mechanisms and temporal response properties. Ethanol exposure continued during the early postnatal period resulted in more profound changes in these measures. Possible biochemical mechanisms include, but are not limited to, reduced rhodopsin concentrations secondary to systemic vitamin A and zinc deficiency and changes in the extracellular potassium concentration due to retinal membrane alterations.