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ACCEPTED MANUSCRIPT current study is consistent with these results, and although we did not detect a higher level of ATP production in 670nm light-treated Müller cells, higher levels of ∆Ψm and COX5a were observed in this study. Therefore, we speculate that ATP production is a consequence of up- regulated ∆Ψm and COX5a. PBM is known to potentially influence cellular DNA and RNA synthesis (Karu, 1999). As photoacceptors are located in the mitochondria, Karu et al. proposed that mitochondrial retrograde signalling can be triggered with PBM (Karu, 2008). PBM-induced changes in ∆Ψm, ROS, and calcium mobilization may be associated with mitochondrial retrograde signalling that leads to modifications in DNA and RNA expression in the nucleus. A growing body of evidence suggests that increased ∆Ψm is related to changes in gene expression. Gavish and colleagues reported an increase in ∆Ψm in human keratinocytes immediately after exposure to 780nm light with a subsequent reduction in IL-6 gene expression 2 hours later (Gavish et al., 2004). Treatment with an inhibitor of the electron transport chain abolished PBM-induced gene expression changes in fibroblasts following irradiation with 760nm or 1140nm light (Schroeder et al., 2007). Therefore, our data strongly support the hypothesis that PBM stimulates mitochondrial retrograde signaling providing further insight into the cellular mechanisms underlying PBM. The understanding of these mechanisms are crucial in the efforts to transition light-based therapy (PBM) from experimental models to clinical acceptance and clinical applications. 5. Conclusions Our findings suggest that 670nm light can directly affect Müller cells and mitigate stress-induced inflammation, which subsequently can reduce microglia/macrophage activation and recruitment. Further, the maintenance of mitochondrial function in Müller cells may enhance their tissue support functions, and thereby contribute to the neuro-protective effects of 670nm light. These data suggest that 670nm light plays a key role in controlling 20 ACCEPTED MANUSCRIPTPDF Image | Photobiomodulation with 670 nm light ameliorates retinal
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