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 s tate of the catecholamine system, especially a reduction in the activi ty of tyrosine hydroxylase (TH), the rate-limiting enzyme of catechola mine synthesis. Here we report on a lead-induced decrease in TH-conten t in neurones of the rhesus monkey retina. Rhesus monkeys were pre- an d postnatally exposed to 0, 350, or 600 ppm of lead acetate (Pb) in th e diet over 9 years. Lead exposure was followed by a 35-month period o f lead-free diet. During this period, blood lead levels of the treated animals declined to nearly those of the untreated controls. Subsequen tly the animals were sacrificed and the retinas processed for TH immun ocytochemistry. The fluorescent dye FITC was used to visualise the ant ibody reaction. Photometric measurements of the fluorescence intensity of stained neurones were made with a laser scanning microscope. In th e rhesus monkey retina two types of TH-immunoreactive neurones are pre sent. In the bright fluorescent type, lead exposure resulted in decrea sed fluorescence intensify and altered the intensity profile of the TH -immunoreactive cells in a dose-dependent manner. In these cells, fluo rescence intensity was 0.53 and 0.22 for 350 ppm Pb and 600 ppm Pb res pectively when the fluorescence in tensity of the untreated controls ( 0 ppm Pb) is taken as 1. Both lead doses also reduced the number of as cending fibres in the inner nuclear layer and the dense staining of fi bres in sublayer 7 of the inner plexiform layer. The weakly fluorescen t cell type disappeared to a large extent under 350 ppm Pb treatment a nd 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 ef fect persists beyond the end of exposure. (C) 1997 Inter Press, Inc.