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S. Y. Chaney, A. Giddabasappa, J. E. Johnson, D. A. Fox; Spatiotemporal Delays in Retinal Glutaminergic Development Are Produced by Gestational Lead Exposure (GLE). Invest. Ophthalmol. Vis. Sci. 2008;49(13):5900. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we showed that GLE increased and prolonged the proliferation of retinal progenitor cells (RPCs) resulting in a 30% increase in late-born rods and bipolar cells, but not Müller glial cells [ARVO 2007]. While the molecular basis of this novel retinal phenotype is being investigated [ARVO 2008], little is known about its functional development. Our present goal was to examine the spatiotemporal and lamination patterns of early developing rods, bipolar cells and Müller glial cells.
C57BL/6 female mice were exposed to water or lead throughout gestation (E) and until postnatal day (PN) 10: a period equivalent to human gestation. At E18.5, PN1, PN3, PN5, PN7 and PN10 fixed-frozen vertical sections from central retina were processed for confocal immunocytochemistry using well-characterized antibodies.
In the distal neuroblastic layer of control retinas, the onset of recoverin and rhodopsin expression occurred at E18.5, whereas recoverin and rhodopsin neurite projections first appeared at E18.5 and PN1, respectively. In GLE retinas, rhodopsin expression and neurite onset were delayed 2-3 days. By PN3, the number of double-labeled rhodopsin-positive and recoverin-positive rods was increased significantly in GLE retinas. In control retinas, vesicular glutamate transporter 1 (VGlut1) labeling of the outer plexiform layer (OPL) was: punctate at PN3; laminated in cones by PN5 and rods by PN7; and intense in cones at PN7 and rods at PN10. In GLE compared to control retinas, VGlut1 OPL labeling was: not present at PN3; decreased in cones at PN5 and PN7; absent in PN7 rods and reduced in PN10 rods. In control retinas, VGlut1 labeled inner plexiform layer sublaminae a (IPLa) weakly at PN7 and both IPLa and IPLb strongly at PN10. In GLE retinas, VGlut1 labeled IPLa minimally at PN7 and normally at PN10, and IPLb minimally at PN10. In control and GLE retinas, glutamine synthetase labeled proximal Müller glial cell processes strongly by PN5 and distal processes by PN10.
GLE delayed early rod, but not cone (recoverin), expression; rod and cone synaptic terminal lamination and development; and OFF (IPLa) and ON (IPLb) bipolar cell synaptic terminal development. The functional consequences of these GLE-induced spatiotemporal delays in glutamatergic development, and likely neurotransmission, during RPC proliferation and cell fate specification may underlie the observed increase in late-born rods and bipolar cells.
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