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ACCEPTED MANUSCRIPT The inflammasome has been linked to the progression of retinal degenerations such as AMD (Doyle et al., 2012a; Tarallo et al., 2012), and generation of IL-1β is one of the direct consequences of NLRP3 inflammasome activation (Ambati et al., 2013; Schroder and Tschopp, 2010). In the current study, we demonstrated that the irradiation of Müller cells with 670nm light leads to down-regulation of IL-1β in response to PD. However, it does not influence the expression of the NLRP3 inflammasome in these cells, indicating that the production of IL-1β may be inflammasome-independent in some retinal cell types (Netea et al., 2015). Our results showed that Müller cells are not major contributors to inflammasome activation, further supporting the view that the RPE and microglia/macrophages are the primary sites of inflammasomes (Doyle et al., 2012b; Kataoka et al., 2015; Kauppinen et al., 2016; Tseng et al., 2013). 4.3 670nm light increased COX5a expression and elevated ∆Ψm We have shown that 670nm light treatment leads to an increase in Rlbp1 in Müller cells. RLBP1 is required for the maintenance of normal metabolic function (Taylor et al., 2015), so the increase towards control levels suggests that treatment with 670nm light supports Müller cells in maintaining normal cellular functions, to withstand tissue stress caused by PD and to protect photoreceptors. In addition, we also found that the treatment with 670nm light increased the ∆Ψm and expression of COX5a in Müller cells under PD. COX is complex IV of the mitochondrial respiratory chain, known to absorb energy from far red to near infrared light (Schroeder et al., 2007). This can trigger a higher ∆Ψm, which generates ATP in cells (Verardo et al., 2008). Kaynezhad and colleagues reported that 670nm light increased the level of oxidized COX, for 1-2 hours after a single 5-minute exposure (Kaynezhad et al., 2016). Elevated production of ATP and higher protein expression of COX were observed in models of retinal degeneration. The ∆Ψm was increased in RPE cells in response to 670nm light in aged mice (Begum et al., 2013; Kokkinopoulos et al., 2013b). The 19 ACCEPTED MANUSCRIPTPDF Image | Photobiomodulation with 670 nm light ameliorates retinal
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