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N Cuenca, H Kolb, A Angulo, E de Juan, S Lopez, C Barcia, M Herrero; Experimental Parkinson's Disease in Long-term Treated Monkeys Causes Changes in Certain Amacrine Cell Morphologies and Population Densities in the Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2769.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathological changes in experimental animals reminiscent of those that occur in idiopathic Parkinson's disease. There is evidence that visual abnormalities in Parkinson's disease are due to disruption of dopaminergic pathways in the retina. Here we try to determine whether MPTP alters the tyrosine hydroxylase (TH) immunoreactive, dopaminergic retinal amacrine cells (DA), and other amacrine cells with which the DA cells are known to synapse. Methods:Adult monkeys (Macaca fascicularis) were treated with cumulative doses of MPTP ranging from 0.5 to 5 mg/kg for up to 4 years.. Paraformaldehyde-fixed retinal wholemounts and cross sections were immunostained with antibodies against tyrosine hydroxylase (TH) and calretinin (CR). We also performed histochemistry for NADPH-diaphorase. Double immunostained sections and wholemount labeled retinas were examined by confocal microscopy. Results:After 4 years of dopamine depletion we detected changes in the retinas of the experimental monkeys. We saw an increase of dopamine cell density in central retina. At the same time we saw a distinct loss of both numbers of processes and branching complexity of the dopamine cells in stratum S1 of the IPL. Concurrently, we found an increase in the density of CR-labeled cells in the MPTP-treated retinas compared to normal retinas. CR-IR AII amacrine cells appeared to have a marked decrease in number of their lobular appendages full of mitochondrias. In addition, NADPH-diaphorase positive amacrine cells, which we consider to be NO containing amacrine cells, underwent a similar density increase as the DA cell population. Conclusion:The present data suggests that AII and nNOS amacrine cells are sensitive to dopamine depletion. There appears to be upregulation of calretinin and NADPH-diaphorase in perhaps other cell types than are normally visible with these markers and at the same time the normally postsynaptic cell to the dopamine cell, i.e. the AII amacrine cell, is changing its morphology at the site of dopaminergic synaptic input to its cell body and lobular appendages. A definite affect on retinal circuitry must be happening in Parkinson's disease. Support: DGESIC PB98-0972.
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