Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.
Fox-DA; Hamilton-WR; Johnson-JE; Xiao-W; Chaney-S; Mukherjee-S; Miller-DB; O'Callaghan-JP
Toxicol Appl Pharmacol 2011 Nov; 256(3):258-267
Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was = 1, = 10, ~25 and ~40 µg/dL, respectively, on PN10 and by PN30 all were = 1 µg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity.
Humans; Children; Birth-defects; Lead-absorption; Laboratory-animals; Neurotoxins; Neurotoxic-effects; Environmental-exposure; Exposure-levels; Exposure-limits; Risk-factors; Brain-disorders; Eye-disorders; Retinal-disorders; Cell-damage; Cell-function;
Author Keywords: Lead; Gestational exposure; Retina; Amacrine cells; Dopamine; Cell loss
Donald A. Fox, University of Houston, College of Optometry, 4901 Calhoun Road, Houston, TX 77204-2020
Healthcare and Social Assistance; Transportation, Warehousing and Utilities
Toxicology and Applied Pharmacology