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CHAPTER 1 Generalised signalling pathway of photobiomodulation using red to NIR light. The light is absorbed by photoacceptors, and ultimately leads to cell proliferation/migration, anti-inflammation, and cytoprotection. 1.2.2.1 Mitochondria based hypotheses The involvement of ATP and cAMP in the signalling pathways has drawn huge attention to the mitochondria, especially the electron transport chain on the mitochondrial membrane. Three decades ago, a study of the action spectra of the rate of DNA synthesis and the absorption spectra of photoacceptors in the respiratory chain, suggested that cytochrome c oxidase (CCO) of the electron transport chain acts as the main photoacceptor in PBM using red to NIR light (Karu, 1989; Karu, 2008; Karu, 2010; Karu and Kolyakov, 2005). Within the ‘optical window’ (Section 1.2.1), there are two regions where the peak rate of DNA synthesis coincides with the peak CCO absorption; one around 670 nm, the other one around 820 nm. By absorbing light energy, CCO activity is increased due to increased availability of electrons (Wu et al., 2014). The extra light energy increases the mitochondrial membrane potential. This causes changes in ATP synthesis, pH and redox potentials which ultimately lead to changes in transcription factors (Karu, 2010). Apart from direct light stimulation of CCO, it is also proposed that light energy can accelerate the dissociation of NO from CCO to increase its activity (Karu et al., 2005). In a normal cell, NO competes with O2 to bind with CCO, therefore inhibiting water and ATP production to regulate energy consumption (Antunes et al., 2004). Following PBM, this NO-dependent inhibition is reversed leading to increased O2 consumption and ATP production. 1.2.2.2 Non-mitochondria based hypotheses Studies in Drosophila vision led to the discovery of a group of photosensitive ion channels called transient receptor potential (TRP) channels (Hardie, 2014). They are mostly located on the plasma membrane, allowing cation influx upon various stimuli such as heat, cold, chemical, hormone, pressure, and light. Of the different families within this TRP group, TRPV (“Vanilloid”) channels have attracted the most attention in the area of PBM. A few studies have tried to investigate the role of TRPV channels during PBM, however, some of the studies used blue (405 nm) to green (532 nm) light (Gu et al., 2012; Yang et al., 2007), which has limited penetration through tissue layers. Other studies used longer wavelengths (1800-2800 nm) in the infrared range (Albert et al., 2012; Ryu et al., 2010), however, infrared is mostly absorbed by water in the tissue to produce heat. While TRPV channels have been shown to be sensitive to temperature and are upregulated by heat (Benham et al., 2003; Hu et al., 2015), there remains a lack of evidence supporting the notion that PBM directly activates TRPV channels which provides other biological effects. However, it has been shown that internal alkalization following photobiomodulation (which occurs in the mitochondria-based hypothesis) could activate TRPV channels (Dhaka et al., 2009). 22PDF Image | Effects of Red Light Treatment on Spinal Cord Injury
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