Electronic Thesis and Dissertation Repository


Master of Science




Dr. Kathleen Hill


Retinal diseases are personally debilitating and expensive, yet many early disease mechanisms leading to their onset and progression remain poorly understood. The harlequin mouse is a model of human mitochondrial dysfunction and parainflammation leading to subsequent cerebellar and retinal degeneration. Diagnosis of retinal degeneration can be tracked in vivo and is associated with AIF dysfunction. Here, retinal dysfunction in the harlequin mouse was first quantified using electroretinography followed by assay of blood-retinal-barrier integrity and transcriptome alterations in young adulthood. Nonmetric multidimensional scaling of oscillatory potentials provided a novel, comprehensive assessment of inner-retinal health and can detect shifts in OP parameters. Barrier integrity ruled out confounding exogenous antigens and confirmed an endogenous source of retinal tissue malfunction. In addition, transcriptome alterations support the necessity of the hq retina to maintain metabolic demands. Alternative metabolism pathways are hypothesized to be important for hq complex I mitochondrial-dysfunction associated retinal degeneration.