Low-Level Human Equivalent Gestational Lead Exposure Produces Supernormal Scotopic Electroretinograms, Increased Retinal Neurogenesis, and Decreased Retinal Dopamine Utilization in Rats

Fox, Donald A.; Kala, Subbarao V.; Hamilton, W. Ryan; Johnson, J. E.; O’Callaghan, James P.

doi:10.1289/ehp.11268

Cited by 32 publications

(41 citation statements)

References 49 publications

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“…One explanation for the delayed response evident in the Pb 2+ -exposed larvae (Fig. 3A) is an increase in the sensory threshold of the lateral line neuromasts, as observed in frog and rat retinal cells exposed to Pb 2+ (Fox et al 2008; Fox et al 1991; Fox and Sillman 1979). Second, depressed neuronal function also may have occurred in the descending interneurons that connect the M-cell to the lateral trunk muscles.…”

Section: Discussionmentioning

confidence: 85%

Developmental lead exposure causes startle response deficits in zebrafish

et al. 2011

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Lead (Pb2+) exposure continues to be an important concern for fish populations. Research is required to assess the long-term behavioral effects of low-level concentrations of Pb2+ and the physiological mechanisms that control those behaviors. Newly fertilized zebrafish embryos (<2 hours post fertilization; hpf) were exposed to one of three concentrations of lead (as PbCl2): 0, 10, or 30 nM until 24 hpf. 1) Response to a mechanosensory stimulus. Individual larvae (168 hpf) were tested for response to a directional, mechanical stimulus. The tap frequency was adjusted to either 1 or 4 taps/sec. Startle response was recorded at 1000 fps. Larvae responded in a concentration-dependent pattern for latency to reaction, maximum turn velocity, time to reach Vmax and escape time. With increasing exposure concentrations, a larger number of larvae failed to respond to even the initial tap and, for those that did respond, ceased responding earlier than control larvae. These differences were more pronounced at a frequency of 4 taps/sec. 2) Response to a visual stimulus. Fish, exposed as embryos (2–24 hpf) to Pb2+ (0–10 uM) were tested as adults under low light conditions (~60 μW/m2) for visual responses to a rotating black bar. Visual responses were significantly degraded at Pb2+ concentrations of 30 nM. These data suggest that zebrafish are viable models for short- and long-term sensorimotor deficits induced by acute, low-level developmental Pb2+ exposures.

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Section: Discussionmentioning

confidence: 85%

Developmental lead exposure causes startle response deficits in zebrafish

et al. 2011

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“…There were no changes in scotopic and photopic ERG a-waves measured either at the peak or at 10 ms. The latter measure is thought to reflect the function of the photoreceptors without the contribution of other retinal cells (Fox et al 2008, Jamison et al 2001). The flicker ERG amplitudes recorded with UV or green lights were unchanged, suggesting that the function of S-cones and M-cones was not altered by toluene.…”

Section: Discussionmentioning

confidence: 99%

“…Parameters analyzed included the peak latencies of the a-wave and b-wave, the a-wave amplitude (measured baseline to peak) and the b-wave amplitude (measured trough-to-peak from a-wave to b-wave). In addition, an alternative measurement of a-wave amplitude was obtained at 10 ms after the flash, which was thought to better reflect the function of only rod photoreceptors prior to the onset of neural activity from other retinal cells (Fox et al 2008, Jamison et al 2001). …”

Section: Methodsmentioning

confidence: 99%

Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long–Evans rats

et al. 2016

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Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1 year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex.

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“…Fox et al (1997) demonstrated that there were age-and dose-dependent decreases in the rod a-wave and b-wave sensitivity and maximum amplitudes without any effect on cones in developmentally and adult lead-exposed rats in a subsequent study [6]. Recently, Fox et al (2008) have reported a dose-dependent effect of gestational lead exposure in rats, with low and moderate dosing causing supernormal scotopic ERGs, in contrast to reduced scotopic ERGs seen after high-level gestational exposure [7]. In adult rats exposed to lead for 3 weeks, qualitatively similar ERG changes occurred in the absence of cell loss or decrease in rhodopsin content [6].…”

Section: Discussionmentioning

confidence: 99%