title: Functional alterations and apoptotic cell death in the retina following developmental or adult lead exposure.
abstract: Long-term visual system deficits occur in man and animals following developmental and occupational lead exposure. Recent experimental data suggests that the adult brain is not altered following lead exposure. Therefore, the aim of these studies was to use the retina as a CNS model to examine and compare the morphological, biochemical and electroretinographic (ERG) changes occurring in rats exposed to low or moderate levels of lead during development (0-21 days of age) with those occurring in adult rats with equivalent blood and retinal levels of lead for three or six weeks. Five main results were obtained. First, developmental and adult lead exposure for six weeks produced age- and dose-dependent retinal degeneration such that rods and bipolar cells were selectively lost. At the ultrastructural level, all dying cells exhibited the classical morphological features of apoptotic cell death. Second, in the lead-exposed groups, the decrease in the number of rods was correlated with the loss of rhodopsin content per eye confirming that rods were directly affected by lead. Third, single-flash rod ERGs and cone ERGs obtained from developmentally and adult lead-exposed rats 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 adult rats exposed to lead for three weeks, qualitatively similar ERG changes occurred in the absence of cell loss or decrease in rhodopsin content. Fourth, developmental and adult lead exposure for three and six weeks produced age- and dose-dependent decreases in retinal cGMP phosphodiesterase (PDE) activity resulting in increased cGMP levels. Fifth, picomolar to micromolar concentration of free lead directly inhibited rat retinal and purified bovine rod cGMP PDE. In summary, there are three main conclusions. First, the retinas of developing and adult rats exposed to lead exhibit qualitatively similar rod-mediated ERG alterations as well as rod and bipolar apoptotic cell death. Thus, developing and mature retinas are both sensitive to the adverse effects of lead: albeit to significantly different extents. Second, a similar biochemical mechanism such as the inhibition of rod and bipolar cell cGMP PDE, varying only in degree and duration, underlies both the lead-induced ERG rod-mediated deficits and the rod and bipolar apoptotic cell death. Third, the composite results from our experiments and those of others suggest that the developing retina might be more sensitive to preweaning lead exposure than the hippocampus and thus may serve as a good model for studying the cellular and molecular mechanisms underlying developmental and adult lead neurotoxicity.
authors.affiliation: College of Optometry and Department of Biochemical and Biophysical Sciences, University of Houston, Texas 77204-6052, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Fox
authors.forename: M L
authors.initials: ML
authors.lastname: Campbell
authors.forename: Y S
authors.initials: YS
authors.lastname: Blocker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007854:Lead / Q000633:toxicity*; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D012160:Retina / Q000187:drug effects*
chemical_list: D007854:Lead