Date of Award
Master of Science
Dr. Kathleen Hill
Although there are many aging-associated retinal diseases, the aging mechanisms which initiate retinal disease remain elusive. To investigate this problem, a model of premature aging, the harlequin mouse, was examined for deficits in retinal function, anatomy and histology, as well as changes in retinal oxidative stress, gene expression and mitochondrial DNA damage. Retinal function of the harlequin mouse, as assessed by electroretinography, was compromised in advance of change in retinal anatomy and histology. Functional deficits occurred in parallel with increased oxidative stress, assessed by in situ dihydroethidium staining. Furthermore, microarray transcriptome analysis of harlequin mice identified markers of mitochondrial stress, inflammation, and retinal remodelling. The random mutation capture assay detected few mitochondrial deletions, indicating minimal relevance of mitochondrial DNA damage to harlequin mitochondrial dysfunction and retinal pathology. These data indicate that DNA-damage- independent mitochondrial dysfunction drives a loss of retina function prior to neuron death in the harlequin model of aging.
Laliberte, Alex Michael, "DNA-damage-independent mitochondrial dysfunction drives a loss of retina function prior to neuron death in the harlequin mouse model of aging" (2010). Digitized Theses. 3749.