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ACCEPTED MANUSCRIPT Treatment with 670nm red light has been shown to reduce inflammation in retinal diseases (Geneva, 2016), however, there is still a lack of understanding of the precise cellular mechanisms underpinning its anti-inflammatory effects. The current study offers insight into cellular signalling pathways influenced by photobiomodulation during retinal degeneration, and demonstrates that treatment with 670nm light reduces Müller cell gliosis and subsequent MG/MΦ activation. Firstly, 670nm light suppressed glial activation by reducing the expression of pro-inflammatory cytokines, chemokines and oxidative stress components in Müller cells exposed to damaged photoreceptors. Secondly, 670nm light reduced activation of MG/MΦ by influencing the expression of inflammatory activators by Müller cells. Thirdly, we demonstrated that a potential mechanism of action of 670nm light is through the support of mitochondrial membrane potential (∆Ψm) to stabilise mitochondrial function, and the improvement of metabolic function in stressed Müller cells. 4.1 670nm light modulates Müller cell reactive gliosis In our earlier in vivo studies, we found that 670nm treatment reduced photoreceptor death following PD, and mitigated Müller cell stress (Albarracin et al., 2011; Albarracin and Valter, 2012). However, what remained unclear was whether 670nm light directly regulates Müller cell stress, or indirectly influences their activation through the damaged photoreceptors (Abrahan et al., 2009). In the current study, as only Müller cells were exposed to 670nm light, we were able to isolate the direct effects of 670nm on these macroglia. We show that treatment with 670nm light reduces Müller cell stress in isolated cells, as evidenced by their reduced expression of Gfap following PD, which is consistent with previous in vivo studies using PD (Albarracin et al., 2011; Marco et al., 2013) and ageing (Begum et al., 2013). GFAP is a well-known marker of Müller cell stress and gliosis in retinal diseases (Albarracin et al., 2011; Bringmann et al., 2009; Bringmann et al., 2006; 17 ACCEPTED MANUSCRIPTPDF Image | Photobiomodulation with 670 nm light ameliorates retinal
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