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ACCEPTED MANUSCRIPT Keywords: Müller cells; 670nm light; photobiomodulation; retinal degeneration; oxidative stress; macrophages; inflammation; microglia 1. Introduction Irradiation with low energy light wavelengths from far red to the near infrared spectrum (600nm-1000nm), termed as PBM, has been shown to display beneficial effects on various tissue injuries (Albarracin et al., 2011; Albarracin et al., 2013; Wong-Riley et al., 2005), such as accelerated wound healing in skin, decreased pain perception in joint disorders (Herranz-Aparicio et al., 2013) and reduced inflammation in autoimmune diseases (Brosseau et al., 2005). PBM has also been used to reduce neuroinflammation in rodent models of brain damage and spinal cord injury (Giacci et al., 2014; Hu et al., 2016). PBM has been shown to be beneficial in human retinal diseases and animal models of age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinitis pigmentosa (RP) (Abrahan et al., 2009; Albarracin et al., 2011; Geneva, 2016). It is proposed that cytochrome c oxidase (COX), the rate-limiting enzyme in terminal phosphorylation in the mitochondrial respiratory chain, is the most likely primary photoacceptor of 670nm light (Desmet et al., 2006; Karu, 1999). Exposure to 670nm light has shown to enhance COX activity in retinas (Begum et al., 2013; Kaynezhad et al., 2016) and primary neurons (Desmet et al., 2006; Wong-Riley et al., 2005), mediate the increase of redox states in mitochondria (Kaynezhad et al., 2016), increase ATP production (Calaza et al., 2015; Gkotsi et al., 2014; Wong-Riley et al., 2005) and up-regulate mitochondrial membrane potential (∆Ψm) (Kokkinopoulos et al., 2013b). One of the beneficial effects of treatment with 670nm light is the apparent reduction of oxidative stress and the mitigation of the subsequent inflammatory response in the retina both of which are key features of several retinal diseases including AMD and DR (Tang et al., 2013; Whitcup et al., 2013). 4 ACCEPTED MANUSCRIPTPDF Image | Photobiomodulation with 670 nm light ameliorates retinal
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