Date of Award
Doctor of Philosophy
Janis T. Eells
Joseph Carroll, Jeri-Anne Lyons, Dean T. Nardelli, Wendy E. Huddleston, Mahsa Ranji, Thomas B. Connor, Jr.
Cytochrome C Oxidase, Mitochondrial Dysfunction, Near-Infrared Light, Photobiomodulation
The retinal degenerative disease, retinitis pigmentosa (RP), is the most common cause of inherited blindness in the developed world and is caused by the progressive degeneration of rod photoreceptor cells preceding cone degeneration. Mitochondrial dysfunction and oxidative stress have been shown to play a significant role in the pathogenesis of RP and other retinal degenerative diseases. A growing body of evidence indicates that exposure of tissue to low energy photon irradiation in the far-red to near-infrared (NIR) range of the spectrum, (photobiomodulation or PBM) acts on mitochondria-mediated signaling pathways to attenuate oxidative stress and prevent cell death. These studies tested the hypothesis that PBM acts in the retina to promote mitochondrial integrity and function, prevent photoreceptor cell death and preserve retinal function in an established rodent model of retinitis pigmentosa, the P23H rhodopsin transgenic rat. Retinal function, structural integrity, surviving photoreceptors and the mitochondrial redox state were assessed using electroretinography, spectral domain optical coherence tomography, histomorphometry and cryofluorescence redox imaging. PBM did not alter the structural and functional characteristics of retina in a non-dystrophic animal strongly supporting the safety of PBM. Establishing the safety of PBM is essential to advance the therapy to clinical use. 830 nm PBM exerted a robust retinoprotective effect compared to 670 nm PBM in the P23H transgenic rat model. 830 nm PBM during the critical period of photoreceptor degeneration in P23H transgenic rat profoundly attenuated retinal degeneration resulting in the preservation of retinal function; retinal morphology and retinal metabolic state in comparison to the sham-treated group. An in vivo longitudinal study corroborated the structural preservation observed in the cross-sectional study. These findings provide evidence supporting the therapeutic utility of PBM in the treatment of retinal degenerative disease. They also further our understanding of the mechanism of action of PBM by showing that it improves mitochondrial function in the retinae of RP animals. By exploiting, the cells own mechanism of self-repair, PBM has the potential for translating into clinical practice as an innovative, non-invasive stand-alone or adjunct therapy for the prevention and treatment of retinal diseases.
Gopalakrishnan, Sandeep, "Photobiomodulation in Inherited Retinal Degeneration" (2012). Theses and Dissertations. Paper 4.