Fox D A, Farber D B
College of Optometry, University of Houston, TX 77004.
Exp Eye Res. 1988 Apr;46(4):597-611. doi: 10.1016/s0014-4835(88)80016-2.
In vitro studies have demonstrated that lead selectively and reversibly depresses the rod photoreceptor component of the electroretinogram (ERG). To determine if low-level lead exposure during early postnatal development produced long-term selective rod deficits, we examined rod and cone ERG functions and cyclic GMP and cyclic AMP metabolism in adult control and lead-exposed rats. A-wave and b-wave voltage-log intensity and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, revealed that low-level lead exposure during early postnatal development caused a 23- and 18% decrease in maximum amplitude, a 1.0- and 0.5 log unit decrease in absolute sensitivity and a mean latency increase of 47- and 29%, respectively. Additional ERG experiments, using scotopically balanced stimuli and scotopic and photopic flicker fusion frequency functions, also demonstrated selective rod deficits. Cone ERGs, elicited by 30-Hz white flashes in the presence of a white background adapting light, were similar in control and lead-exposed rats. Lead exposure during early postnatal development caused cGMP levels in dark-adapted and light-adapted retinas to increase 40- and 25%, respectively, above controls whereas cyclic AMP levels remained unchanged. Light-activated cyclic GMP phosphodiesterase (cGMP-PDE) was inhibited 40% while guanylate cyclase activity was unchanged. The retinal lead concentration was 10(-6) M at the end of exposure (day 21) while at the time of ERG testing and biochemical analysis it was 10(-7) M. In vitro studies with adult control retinas incubated with 10(-9)-10(-4) M lead revealed a dose-response inhibition (10-40%) of cGMP-PDE between 10(-6)- and 10(-4) M lead and stimulation of guanylate cyclase (20-158%) only above 10(-4) M lead, indicating that cGMP-PDE is more sensitive to the direct effects of lead than the synthetic cGMP enzyme. These in vitro cyclic nucleotide metabolism results are similar to those we observed in vivo and both are consistent with the observed ERG changes. The selective rod-mediated amplitude, sensitivity and temporal deficits and the lack of effect on the cone ERGs clearly demonstrate that low-level lead exposure during early postnatal development causes a long-term selective disruption of rat rod photoreceptors. The relevance and applicability of these data to subclinical pediatric lead poisoning has yet to be established.
体外研究表明，铅可选择性且可逆地抑制视网膜电图（ERG）的视杆光感受器成分。为了确定出生后早期发育期间的低水平铅暴露是否会导致长期的选择性视杆缺陷，我们检测了成年对照大鼠和铅暴露大鼠的视杆和视锥ERG功能以及环鸟苷酸（cGMP）和环腺苷酸（cAMP）代谢。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-对数强度以及潜伏期-对数强度函数显示，出生后早期发育期间的低水平铅暴露导致最大振幅分别降低23%和18%，绝对敏感度分别降低1.0和0.5对数单位，平均潜伏期分别增加47%和29%。使用暗视平衡刺激以及暗视和明视闪烁融合频率函数的其他ERG实验也证明了选择性视杆缺陷。在白色背景适应光存在下，由30 Hz白色闪光诱发的视锥ERG在对照大鼠和铅暴露大鼠中相似。出生后早期发育期间的铅暴露导致暗适应和明适应视网膜中的cGMP水平分别比对照增加40%和25%，而cAMP水平保持不变。光激活的环鸟苷酸磷酸二酯酶（cGMP-PDE）受到40%的抑制，而鸟苷酸环化酶活性未改变。暴露结束时（第21天）视网膜铅浓度为10^(-6) M，而在进行ERG测试和生化分析时为10^(-7) M。用10^(-9)-10^(-4) M铅孵育成年对照视网膜的体外研究表明，在10^(-6)-10^(-4) M铅之间cGMP-PDE有剂量依赖性抑制（10-40%），仅在高于10^(-4) M铅时鸟苷酸环化酶受到刺激（20-158%），这表明cGMP-PDE对铅的直接作用比合成cGMP酶更敏感。这些体外环核苷酸代谢结果与我们在体内观察到的结果相似，并且两者都与观察到的ERG变化一致。选择性视杆介导的振幅、敏感度和时间缺陷以及对视锥ERG无影响清楚地表明，出生后早期发育期间的低水平铅暴露会导致大鼠视杆光感受器的长期选择性破坏。这些数据与亚临床小儿铅中毒的相关性和适用性尚未确定。
