Persistent decrease of the dopamine-synthesizing enzyme tyrosine hydroxylase in the rhesus monkey retina after chronic lead exposure.
One of the toxic effects of lead in the CNS is an altered functional state of the catecholamine system, especially a reduction in the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Here we report on a lead-induced decrease in TH-content in neurones of the rhesus monkey retina. Rhesus monkeys were pre- and postnatally exposed to 0, 350, or 600 ppm of lead acetate (Pb) in the diet over 9 years. Lead exposure was followed by a 35-month period of lead-free diet. During this period, blood lead levels of the treated animals declined to nearly those of the untreated controls. Subsequently the animals were sacrificed and the retinas processed for TH immunocytochemistry. The fluorescent dye FITC was used to visualise the antibody reaction. Photometric measurements of the fluorescence intensity of stained neurones were made with a laser scanning microscope. In the rhesus monkey retina two types of TH-immunoreactive neurones are present. In the bright fluorescent type, lead exposure resulted in decreased fluorescence intensity and altered the intensity profile of the TH-immunoreactive cells in a dose-dependent manner. In these cells, fluorescence intensity was 0.53 and 0.22 for 350 ppm Pb and 600 ppm Pb respectively when the fluorescence intensity of the untreated controls (0 ppm Pb) is taken as 1. Both lead doses also reduced the number of ascending fibres in the inner nuclear layer and the dense staining of fibres in sublayer 1 of the inner plexiform layer. The weakly fluorescent cell type disappeared to a large extent under 350 ppm Pb treatment and was not detectable in the 600 ppm Pb group. The results demonstrate that lead exposure affects the dopaminergic retinal amacrine cells by reducing the TH-content in these neurones and that this neurotoxic effect persists beyond the end of exposure.
Kohler
K
K
Department of Pathophysiology of Vision and Neuroophthalmology, University Eye Hospital, Tübingen, Germany.
Lilienthal
H
H
Guenther
E
E
Winneke
G
G
Zrenner
E
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007854:Lead / Q000633:toxicity*; D008253:Macaca mulatta; D012160:Retina / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects*
D007854:Lead; D014446:Tyrosine 3-Monooxygenase