Fox D A, Katz L M, Farber D B
College of Optometry, Department of Biochemical and Biophysical Sciences, University of Houston, Texas 77204-6052.
Neurotoxicology. 1991 Winter;12(4):641-54.
Electroretinographic (ERG), morphometric and biochemical studies on retinas from monkeys or rats reveal that moderate level developmental lead (Pb) exposure produces long-term selective rod deficits and degeneration. The present studies determined whether similar alterations occur following low level developmental Pb exposure. Long-Evans rats, exposed to Pb only via dam's milk from parturition to weaning, had mean blood Pb of 18.8 micrograms/dl at weaning and 6.6 micrograms/dl at 90 days of age. Morphometric and ultrastructural studies revealed no signs of rod loss or degeneration although the presence of glycogen in some rod mitochondria suggests the occurrence of a metabolic dysfunction. Retinal sensitivity and rhodopsin content per eye were decreased in a manner such that, they followed the established log-linear relationship. A- and b-wave voltage- and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, revealed that low level Pb exposure caused a 25% and 15% decrease in mean amplitude, a 0.5 and a 0.5 log unit decrease in absolute sensitivity, and a 23% and 16% increase in mean latency, respectively. Scotopic (rod-mediated) and photopic (cone-mediated) flicker fusion frequency measures revealed selective rod deficits. Adult rats had a 15% inhibition of retinal cGMP-phosphodiesterase resulting in a 19% and 12% increase in cGMP in dark- and light-adapted states, respectively. The above data confirm and extend our previous studies conducted in rats with blood lead levels of 59 micrograms/dl during development. The rhodopsin and cyclic nucleotide metabolism data, as well as our recent data showing an inhibition of retinal Na+, K(+)-ATPase, are entirely consistent with the observed ERG changes. The fact that rat rods are similar to monkey and human rods suggests the relevance and applicability of these data to low level pediatric Pb poisoning. Thus, these data suggest that alterations in rod sensitivity and temporal processing may occur in children exposed to low levels of lead during perinatal development.
对猴子或大鼠视网膜进行的视网膜电图（ERG）、形态学和生化研究表明，发育阶段中等程度的铅（Pb）暴露会导致长期的选择性视杆细胞缺陷和退化。本研究确定了发育阶段低水平的铅暴露后是否会出现类似的改变。长 Evans 大鼠从分娩到断奶仅通过母乳接触铅，断奶时平均血铅水平为 18.8 微克/分升，90 日龄时为 6.6 微克/分升。形态学和超微结构研究未发现视杆细胞丢失或退化的迹象，尽管在一些视杆细胞线粒体中存在糖原表明发生了代谢功能障碍。每只眼睛的视网膜敏感度和视紫红质含量以一种方式降低，即它们遵循既定的对数线性关系。在完全暗适应的大鼠中，由单次闪光 ERG 产生的 a 波和 b 波电压及潜伏期-对数强度函数显示，低水平的铅暴露分别导致平均振幅降低 25%和 15%，绝对敏感度降低 0.5 和 0.5 对数单位，平均潜伏期分别增加 23%和 16%。暗视（视杆细胞介导）和明视（视锥细胞介导）闪烁融合频率测量显示存在选择性视杆细胞缺陷。成年大鼠视网膜 cGMP 磷酸二酯酶受到 15%的抑制，导致在暗适应和明适应状态下 cGMP 分别增加 19%和 12%。上述数据证实并扩展了我们之前在发育过程中血铅水平为 59 微克/分升的大鼠中进行的研究。视紫红质和环核苷酸代谢数据，以及我们最近显示视网膜 Na+、K(+)-ATP 酶受到抑制的数据，与观察到的 ERG 变化完全一致。大鼠视杆细胞与猴子和人类视杆细胞相似这一事实表明这些数据与低水平儿童铅中毒的相关性和适用性。因此，这些数据表明，围产期发育期间暴露于低水平铅的儿童可能会出现视杆细胞敏感度和时间处理的改变。
