Photobiomodulation for the Treatment of Retinal Injury and Retinal Degenerative Diseases

ACKNOWLEDGEMENTS: We gratefully acknowledge Quantum Devices, Inc. (Barneveld, WI) for providing light emitting diode arrays with Quantum's High-Emissivity Aluminiferous Light-Emitting Substrate (HEALS®) technology for this project. Abstract Retinal injury and retinal degenerative diseases are a leading causes of visual impairment in the developed world. Mitochondrial dysfunction and oxidative stress play key roles in the pathogenesis of retinal injury and disease. The development and testing of strategies designed to improve mitochondrial function and attenuate oxidative stress are essential for combating retinal disease. One strategy involves the use of photobiomodulation. Photobiomodulation, low-energy photon irradiation by light in the far-red to near-infrared (NIR) range using low energy lasers or light-emitting diode (LED) arrays, has been applied clinically in the treatment soft tissue injuries and acceleration of wound healing for more than 30 years. The therapeutic effects of photobiomodulation have been hypothesized to be mediated by intracellular signaling mechanisms triggered by the interaction of far-red to NIR photons with the mitochondrial photoacceptor molecule cytochrome oxidase which culminate in improved mitochondrial energy metabolism, increased synthesis of cytoprotective factors and cell survival. The therapeutic potential of 670 nm LED photobiomodulation administered once per day at a fluence of 4 J/cm 2 was investigated in established experimental models of retinal injury, retinal toxicity and retinal disease. Photobiomodulation stimulated retinal wound healing following high-intensity laser-induced retinal injury. Photobiomodulation not only enhanced the rate of wound healing, it also prevented the loss of retinal and cortical visual function induced by laser-induced retinal injury. In a rodent model of retinal mitochondrial toxicity, photobiomodulation preserved retinal function and prevented photoreceptor damage. Moreover, molecular studies revealed that photobiomodulation induced significant upregulation of gene expression pathways involved in mitochondrial energy production and cytoprotection in the retina. Retinitis pigmentosa is the leading cause of vision loss due to retinal degeneration. Photobiomodulation administered during the critical period of photoreceptor development in a rat model of retinitis pigmentosa increased retinal mitochondrial cytochrome oxidase activity, upregulated the production of retinal antioxidants, increased the production of retinal neurotrophic factors and prevented photoreceptor cell death. The molecular, biochemical and functional insights obtained from this research provide crucial information needed for a comprehensive FDA approval for the use of photobiomodulation in the treatment of retinal diseases. From a basic science perspective, they substantiate previous in vitro investigations and support the hypothesis that photobiomodulation augments mitochondrial function and stimulates cytoprotective pathways to prevent retinal damage. From a clinical perspective, they document …