Dopamine Depletion in the Retina of Parkinsonian, MPTP-treated Monkeys Impairs Electrical Synapses and AII Amacrine Cell Morphology

Abstract

Abstract: : Purpose: Psychophysical and electrophysiological studies have shown the existence of a number of visual dysfunctions associated to Parkinson’s disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduces clinical, neurochemical and neuropathological features of idiopathic parkinsonism. There is evidence that visual abnormalities in Parkinson's disease are due to disruption of dopaminergic pathways in the retina. We have investigated whether the lack of dopaminergic processes elicits changes in the main postsynaptic neurons in the monkey retina. Methods: 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), calretinin (CR), connexin36, GABA and glycine. Double immunostained sections and wholemount labeled retinas were examined by confocal microscopy. Results: After 4 years of dopamine depletion we detected morphological changes in the retinas of the experimental monkeys. We saw a loss of both the number of processes and branching complexity of the dopamine cells in stratum S1 of the inner nuclear layer (IPL). CR- immunoreactive AII amacrine cells appeared to have a marked decrease in the number of lobular appendages full of mitochondria. Concurrently, we found a decrease in the density of connexin36-immunoreactive tips in the IPL in MPTP-treated retinas as compared to normal retinas. The number of GABAergic and glycinergic amacrine cells and the IPL immunoreactive layer thickness were also found to be diminished. Conclusion: Present data suggest that dopamine depletion promotes a loss of lobular appendages in AII amacrine cells and a decrease in the number of gap junctions and the levels of inhibitory neurotransmitters. These results show that electrical synapses and postsynaptic neurons are impaired in MPTP-treated retinas and hence could be a cause of visual dysfunctions associated to Parkinson’s disease. Support: DGESIC PB98-0972 and Generalitat Valenciana CTIDIB/2002/146.

Keywords: dopamine • retina: proximal(bipolar, amacrine, and gangli • visual impairment: neuro-ophthalmological dise