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J.E. Johnson, A. Giddabasappa, Q. Chen, D.A. Fox; Mouse Retinal Dopaminergic Amacrine Cell Density and Distribution Are Selectively Altered by Gestational Lead Exposure . Invest. Ophthalmol. Vis. Sci. 2005;46(13):567.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Gestational lead (Pb) exposure produces novel and persistent increases in the rod–mediated ERG a–wave and b–wave amplitudes in children, monkeys and rats. In animals it also produces decreases in retinal tyrosine hydroxylase (TH) immunofluorescence and dopamine (DA) metabolism. Our goals were to develop a clinically relevant mouse model of gestational Pb exposure and to use histological and immunocytochemical techniques to examine the retinas of these mice. Methods: C57BL/6 female mice were exposed to tap water or one of two different Pb drinking solutions two weeks prior to mating, throughout pregnancy and then until postnatal day 10 (PN10): an exposure equivalent to the human gestation period. PN60 mouse retinas were fixed and processed for standard plastic sections, vertical cryostat sections or retinal whole mounts and then examined using light, electron, epifluorescent and laser scanning confocal microscopy to determine the overall density and distribution of: 1) amacrine cells (ACs), 2) TH–positive DA ACs, 3) glycinergic AII ACs using the Disabled 1 (Dab–1) antibody, 4) GABAergic ACs using the glutamate dehydrogenase (GAD65) antibody, and 5) cholinergic starburst ACs using the choline acetyltransferase (ChAT) antibody. Results: At PN10, the mean blood Pb concentration [BPb] in controls and the Pb groups were <1, 10 and 22 µg/dL. At PN60, [BPb] was similar (∼1 µg/dL) in all groups. The density and immunostaining pattern of Dab–1, GAD65, ChAT and morphologically–identified ACs were similar in control and Pb–exposed mice. In control retinas, the number of DA ACs was uniform across the retina (22–25 cells/sq. mm). In the Pb–exposed mice the density of DA ACs and the number of TH–positive dendrites ramifying in sublamina 1 were significantly decreased. In addition, the decrease in DA ACs cells was not uniform across the retina: larger decreases were observed in the dorsal retina. Conclusions: Our results suggest that gestational Pb exposure produced a selective decrease in DA ACs and altered their dorsal–ventral patterning. These findings are consistent with similarly exposed rats that have decreased retinal DA metabolism and persistent scotopic ERG supernormality. These results suggest that the loss and altered patterning of DA ACs may partially contribute to the ERG supernormality observed in gestationally Pb–exposed children and animals. They also suggest that gestational Pb exposure may be a risk factor for Parkinson’s disease.
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