Date of Award
Master of Science
Veterinary Clinical Sciences
Parkinson’s disease (PD) is characterized by a progressive failure of mitochondrial respiratory function and subsequent loss of dopaminergic neurons, which results in severe neuromuscular deficits. Additionally, patients with PD may have visual function abnormalities. The MitoPark (MP) mouse is an experimental model of PD created by disrupting mitochondrial function in dopamine-producing neurons. MitoPark mice develop motor symptoms of PD, but it is currently unknown whether abnormalities in retinal function and structure exist. The objective of this study was to determine whether the retina of MP mice demonstrates any visual system abnormalities.
Retinal function of 5 symptomatic MP mice, and 5 age-matched wild type (WT) mice was evaluated by full field electroretinography (ERG) at varying light intensities following both dark (scotopic) and light (photopic) adaptation. Comparison between the full field ERG a- and b-wave components of MP and WT mice were performed. Animals were subsequently euthanized and the eyes were prepared for standard histopathologic and immunohistochemical analyses. Immunohistochemistry was performed on retinal tissues using antibodies against Glial Fibrillary Acidic Protein (GFAP) and Tyrosine Hydroxylase (TH), which are markers of retinal stress and dopaminergic cells respectively.
Minor alterations of retinal function were observed in the onset, or implicit time, of b-wave formation in the MP mouse, most notably at the highest intensity of light tested. Further, the MitoPark mouse had smaller wave amplitudes than WT mice, but these observations did not reach statistical significance. The histological analyses show that although retinal thickness tended to be decreased in the MP mouse, there were no obvious differences in retinal architecture or in GFAP and TH staining between the two groups. Using a multivariate linear mixed model which included retinal thickness, implicit time and mouse type (i.e., either MP or WT), MP mice exhibited a significantly shorter b wave implicit time at the highest light intensity tested (10 cd·s/m2) in the scotopic recordings. These results suggest that there are changes in the retinal synaptic architecture of the MP mouse which is both reflected in the retinal thickness and electrical signaling of the retina under conditions which stimulate the rod and cone photoreceptors. It would be beneficial to evaluate more mice to strengthen the general trends observed in this study.
Courtenay Michaela Brines
Brines, Courtenay Michaela, "Evaluation of retinal function and structure in a Parkinson's disease murine model" (2015). Graduate Theses and Dissertations. 14799.