Low-level human equivalent gestational lead exposure produces supernormal scotopic electroretinograms, increased retinal neurogenesis, and decreased retinal dopamine utilization in rats

Postnatal lead exposure in children and animals produces alterations in the visual system primarily characterized by decreases in the rod-mediated (scotopic) electroretinogram (ERG) amplitude (subnormality). In contrast, low-level gestational Pb exposure (GLE) increases the amplitude of scotopic ERGs in children (supernormality). Objectives: The goal of this study was to establish a rat model of human equivalent GLE and to determine dose-response effects on scotopic ERGs and on retinal morphology, biochemistry, and dopamine metabolism in adult offspring.

Low- and moderate-level GLE produced persistent scotopic ERG supernormality due to an increased neurogenesis of cells in the rod signaling pathway and/or decreased dopamine utilization, whereas high-level GLE produced rod-selective toxicity characterized by ERG subnormality. The ERG is a differential and noninvasive biomarker of GLE. The inverted U-shaped dose-response curves reveal the sensitivity and vulnerability of the developing retina to GLE.

We exposed female Long-Evans hooded rats to water containing 0, 27 (low), 55 (moderate), or 109 (high) ppm of Pb beginning 2 weeks before mating, throughout gestation, and until postnatal day (PND) 10. We measured maternal and litter indices, blood Pb concentrations (BPb), retinal Pb concentrations, zinc concentrations, and body weights. On PND90, we performed the retinal experiments.

Peak BPb concentrations were < 1, 12, 24, and 46 microg/dL in control, low-, moderate- and high-level GLE groups, respectively, at PNDs 0-10. ERG supernormality and an increased rod photoreceptor and rod bipolar cell neurogenesis occurred with low- and moderate-level GLE. In contrast, high-level GLE produced ERG subnormality, rod cell loss, and decreased retinal Zn levels. GLE produced dose-dependent decreases in dopamine and its utilization. Conclusions: Low- and moderate-level GLE produced persistent scotopic ERG supernormality due to an increased neurogenesis of cells in the rod signaling pathway and/or decreased dopamine utilization, whereas high-level GLE produced rod-selective toxicity characterized by ERG subnormality. The ERG is a differential and noninvasive biomarker of GLE. The inverted U-shaped dose-response curves reveal the sensitivity and vulnerability of the developing retina to GLE.