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Persistent decrease of the dopamine-synthesizing enzyme tyrosine hydroxylase in the rhesus monkey retina after
K Kohler1, H Lilienthal, E Guenther
1Department of Pathophysiology of Vision and Neuroophthalmology, University Eye Hospital, Tübingen, Germany.
Abstract:
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.
Insights
Lead exposure significantly reduces tyrosine hydroxylase (TH) in rhesus monkey retinal neurons, impacting dopaminergic cells. This neurotoxic effect on TH-content persists even after lead removal.
Area of Science:
- Neuroscience
- Toxicology
- Ophthalmology
Background:
- Lead exposure is a known neurotoxin affecting the central nervous system.
- A key toxic effect involves the catecholamine system, particularly reduced tyrosine hydroxylase (TH) activity.
Purpose of the Study:
- To investigate lead's impact on TH-content in rhesus monkey retinal neurons.
- To determine if lead-induced neurotoxicity in the retina persists after exposure cessation.
Main Methods:
- Rhesus monkeys were exposed to lead acetate (0, 350, 600 ppm) for 9 years, followed by a 35-month lead-free period.
- Retinas were analyzed using TH immunocytochemistry and laser scanning microscopy to quantify fluorescence intensity.
- Changes in TH-immunoreactive neurons and fiber layers were assessed.
Main Results:
- Lead exposure dose-dependently decreased TH-content in bright fluorescent retinal neurons.
- Reduced TH-content persisted even after the lead-free period.
- Lead exposure also decreased ascending fibers and altered inner plexiform layer staining; weakly fluorescent cells were diminished or undetectable.
Conclusions:
- Lead exposure neurotoxically affects dopaminergic retinal amacrine cells by reducing TH-content.
- These neurotoxic effects on retinal TH-content are long-lasting and persist beyond the cessation of lead exposure.