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R. Hamilton, J. E. Johnson, A. Giddabasappa, W. Xiao, M. Wang, L. J. Frishman, D. A. Fox; Differential Expression of GABA Transporters Regulate the GABA-Induced Increase in the Scotopic ERG B-Wave Amplitude of Adult Control and Gestationally Lead-Exposed Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3620.
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© ARVO (1962-2015); The Authors (2016-present)
Gestational lead exposure (GLE) significantly increased the a- and b-wave scotopic ERG amplitude in children, adult monkeys and rats. However, preliminary ERG studies in adult mice following GLE showed that scotopic ERG amplitudes were not significantly different from controls. Our goals were to confirm these preliminary ERG results and to examine possible mechanisms underlying the species difference in the GLE-induced ERG supernormality.
C57BL/6 female mice were exposed to water or 55 ppm lead throughout gestation and until postnatal day 10: equivalent to human gestation period. Scotopic ERGs were assessed in adult control (Con) and GLE mice before and one hour after an intravitreal injection of GABA. Retinal gene expression of adult Con and GLE mice was analyzed by Affymetrix Mouse Genome 430 2.0 Array and validated by RT-qPCR. Confocal studies used vertical fixed-frozen sections and wholemounts from adult Con and GLE mice followed by standard blind-observer stereological techniques.
Scotopic ERG a- and b-wave maximum amplitudes in GLE mice were not significantly larger than in Con mice. In Con and GLE mice, GABA removed the negative and positive scotopic threshold responses. GABA significantly increased the peak b-wave amplitude in Con mice: especially for stimuli that saturated the b-wave. In contrast, no increases in b-wave amplitude were seen in GLE mice. Microarray analysis revealed an upregulation of GABA transporters and GABA receptor subunits in GLE retinas. In GLE mice, there was an increased number of rods and bipolar cells (rod and cone), but no change in the number of GAD65-positive GABAergic, Dab1-positive glycinergic or ChAT-positive cholinergic amacrine cells. GLE mice had an increased expression of vesicular GABA transporter (VGAT) in the inner plexiform layer, but no overall change in GAD65 labeling intensity.
These results suggest that GLE increased VGAT activity in the adult retina without changing the number of GABA-positive cells or GABA synthesis. In GLE mice, an increased synaptic GABA influx would explain the absence of the GABA-induced increase in b-wave amplitude observed in control mice and could underlie the absence of ERG supernormality.
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