UBC Theses and Dissertations
Behavioural assessment of the effects of Human retinal pigment epithelial cell implant on motor deficits of a rodent model of parkinson’s disease Cepeda, Ivan Leonardo
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. PD is a progressive disorder characterized pathologically by preferential degeneration of the dopaminergic neurons in the substantia nigra pars compacta that project to the striatum, and the appearance of intracytoplasmatic inclusions known as Lewy bodies. Progressive loss of the nigro-striatal pathway results in decrease in the concentration of dopamine in the striatum. Clinically, PD is characterized by resting tremor, rigidity, bradykinesia and postural instability. To this day, L-dopa associated with a dopa decarboxylase inhibitor is the most effective symptomatic therapy for PD. However, L-Dopa long-term therapeutic limitations have imposed the need for searching alternative treatments for PD. Neural transplantation offers the possibility to place dopamine-producing cells into the striatum of patients with PD. Retinal pigment epithelial (RPE) cells produce the DA precursor L-dopa, are readily isolated from eyes obtained from eye banks, and can be cultured and expanded in to allow implant in multiple patients from a single donor, and when attached to a gelatin microcarrier (GM) and implanted into the striatum, cause long-term amelioration of parkinsonian motor deficits in human and non-human primates without adverse effects. The advantages of RPE cell implants over other cell options for transplantation as a promising therapy for patients with PD makes it deserving of further study. This study provides evidence that the cylinder test and the tapered ledged beam-walking test are sensitive, reliable, clinically relevant and useful for longitudinal studies of the effects of new therapeutic strategies for PD, and reports the first evidence that intrastriatal implantation of RPE-GM ameliorate deficits in spontaneous forelimb and hindlimb motor behaviour, in both a bilateral and a unilateral 6-OHDA rat model of PD.
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