Fox Donald A, Kala Subbarao V, Hamilton W Ryan, Johnson Jerry E, O'Callaghan James P
College of Optometry, University of Houston, 4901 Calhoun Rd., Houston, TX 77204-2020, USA.
Environ Health Perspect. 2008 May;116(5):618-25. doi: 10.1289/ehp.11268.
Postnatal lead exposure in children and animals produces alterations in the visual system primarily characterized by decreases in the rod-mediated (scotopic) electroretinogram (ERG) amplitude (subnormality). In contrast, low-level gestational Pb exposure (GLE) increases the amplitude of scotopic ERGs in children (supernormality).
The goal of this study was to establish a rat model of human equivalent GLE and to determine dose-response effects on scotopic ERGs and on retinal morphology, biochemistry, and dopamine metabolism in adult offspring.
We exposed female Long-Evans hooded rats to water containing 0, 27 (low), 55 (moderate), or 109 (high) ppm of Pb beginning 2 weeks before mating, throughout gestation, and until postnatal day (PND) 10. We measured maternal and litter indices, blood Pb concentrations (BPb), retinal Pb concentrations, zinc concentrations, and body weights. On PND90, we performed the retinal experiments.
Peak BPb concentrations were < 1, 12, 24, and 46 microg/dL in control, low-, moderate- and high-level GLE groups, respectively, at PNDs 0-10. ERG supernormality and an increased rod photoreceptor and rod bipolar cell neurogenesis occurred with low- and moderate-level GLE. In contrast, high-level GLE produced ERG subnormality, rod cell loss, and decreased retinal Zn levels. GLE produced dose-dependent decreases in dopamine and its utilization.
Low- and moderate-level GLE produced persistent scotopic ERG supernormality due to an increased neurogenesis of cells in the rod signaling pathway and/or decreased dopamine utilization, whereas high-level GLE produced rod-selective toxicity characterized by ERG subnormality. The ERG is a differential and noninvasive biomarker of GLE. The inverted U-shaped dose-response curves reveal the sensitivity and vulnerability of the developing retina to GLE.
儿童和动物出生后铅暴露会导致视觉系统发生改变，主要表现为视杆介导的（暗视）视网膜电图（ERG）振幅降低（低于正常水平）。相比之下，低水平孕期铅暴露（GLE）会增加儿童暗视ERG的振幅（高于正常水平）。
本研究的目的是建立一个与人类等效GLE的大鼠模型，并确定其对成年后代暗视ERG以及视网膜形态、生物化学和多巴胺代谢的剂量反应效应。
在交配前2周开始，直至整个妊娠期以及出生后第10天（PND 10），我们将雌性长-伊文斯带帽大鼠暴露于含0、27（低）、55（中）或109（高）ppm铅的水中。我们测量了母体和窝指数、血铅浓度（BPb）、视网膜铅浓度、锌浓度和体重。在PND 90时，我们进行了视网膜实验。
在PND 0 - 10时，对照组、低水平、中等水平和高水平GLE组的最高BPb浓度分别为<1、12、24和46μg/dL。低水平和中等水平GLE导致ERG高于正常水平，视杆光感受器和视杆双极细胞神经发生增加。相比之下，高水平GLE导致ERG低于正常水平、视杆细胞丢失和视网膜锌水平降低。GLE导致多巴胺及其利用率呈剂量依赖性降低。
低水平和中等水平GLE由于视杆信号通路中细胞神经发生增加和/或多巴胺利用率降低，导致持续性暗视ERG高于正常水平，而高水平GLE导致以ERG低于正常水平为特征的视杆选择性毒性。ERG是GLE的一种差异性和非侵入性生物标志物。倒U形剂量反应曲线揭示了发育中的视网膜对GLE的敏感性和易损性。
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