Abstract
Purpose: :
Systemic injection of MPTP to monkeys elicits the appearance of a parkinsonian syndrome including a set of morphological and functional impairments in the retina. The etiology of idiopathic Parkinson’s disease has been associated with intracellular neuronal oxidative damage. Here we have undertaken a proteomics approach in order to identify proteins differentially expressed in the retina of MPTP-treated, parkinsonian monkeys.
Methods: :
Monkeys (Macaca fascicularis) were treated for 2-3 years with MPTP (0.3 mg/kg, i.v.) and then left untreated for 1 additional year. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labeled with different fluorophores and run pairwise on DIGE gels. Polypeptides showing statistically-significant differences in their expression levels were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF mass spectrometry analysis. Protein database interrogation was performed by using the MASCOT search engine.
Results: :
Out of over 700 protein spots resolved on 2D DIGE gels, ca. 30 polypeptides were detected to show a significant underexpression in the parkinsonian monkey retina, whereas one polypeptide was found overexpressed. Their peptide mass fingerprints obtained by MALDI-TOF were used to search the NCBInr database. A number of the identified differentially-expressed polypeptides corresponded to proteins involved in NO toxicity and cellular energy metabolism.
Conclusions: :
We have identified in the MPTP monkey model of idiopathic Parkinson’s disease a set of retinal proteins showing abnormal expression levels in comparison with healthy subjects, in most cases being downregulated. A number of them could be related to an impairment in energy metabolism and oxidative damage, in keeping with one of the prevalent molecular mechanisms underlying the etiology of parkinsonism.
Keywords: retina • proteomics • degenerations/dystrophies