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Changes in Retinal Mitochondrial Function in Ocular Diseases and a Potential Treatment Using Near-Infrared Light

  • Author / Creator
    Han, Woo Hyun
  • Mitochondria are both prominent target and source of reactive oxygen species (ROS). Their role in a wide range of diseases has been gaining a substantial amount of interest, including a number of high-profile ocular diseases. In the present thesis, we investigated the mitochondrial functional changes in animal models of Diabetic Retinopathy (DR) and Stargardt-like Disease (STGD3). Subsequently, we examined a non-invasive therapy, photobiomodulation (PBM), which uses near-infrared light to reportedly increase mitochondrial complex IV (CIV) function and produce positive therapeutic effects. We demonstrate that the OROBOROS Oxygraph-2k high-resolution respirometer can be successfully utilized to study the ocular mitochondrial function in rodent models. Furthermore, we report an early change in retinal mitochondria function in Nile grass rat model of DR; in 2mo – almost a full year before any vascular or functional changes and 4mo before the development of systemic hyperglycemia – the retinal mitochondria showed diminished outer membrane integrity and upregulated NADH-pathway respiration. In contrast, the RPE mitochondria studied in ELOVL4 transgenic model of C57 mice showed preserved mitochondrial function until 10mo after the onset of photoreceptor cell death. These results suggest that in DR, the retinal mitochondria likely play causal role whereas in STGD3, they take the role of a target. Lastly, we report decreased CIV function and increased chemical background respiration in response to a single application of 670nm light. To explain our result, we propose a model of PBM’s mechanisms involving increased nitric oxide release, increased CIV inhibitor resistance, and decreased non-mitochondrial oxygen consumption. In light of this preliminary data, we present a rationale for possible application of PBM in the treatment of DR and STGD3.

  • Subjects / Keywords
  • Graduation date
    Fall 2018
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3668914X
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.